Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
Sponsor
Radiation Therapy Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00304031
Collaborator
National Cancer Institute (NCI) (NIH), European Organisation for Research and Treatment of Cancer - EORTC (Other), NRG Oncology (Other)
1,173
351
3
131
3.3
0
Study Details
Study Description
Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known which schedule of temozolomide when given together with radiation therapy is more effective in treating glioblastoma or gliosarcoma.
PURPOSE: This randomized phase III trial is studying two different schedules of temozolomide to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed glioblastoma or gliosarcoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
Primary
- Determine if dose-intensifying (increasing the "dose-density") the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by overall survival of patients with newly diagnosed glioblastoma or gliosarcoma.
Secondary
-
Determine if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy as measured by progression-free survival.
-
Determine in patients with unmethylated MGMT (O-6-methylguanine-DNA methyltransferase) if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.
-
Determine in patients with methylated MGMT if dose-intensifying the adjuvant temozolomide component of the chemoradiation treatment enhances treatment efficacy (overall and progression-free survival) compared with patients receiving conventional temozolomide dosing.
-
Determine if there is an association between tumor MGMT gene methylation status and treatment response.
-
Compare and record the toxicities of the conventional and dose-intense chemotherapy regimens.
-
Evaluate whether 6-month progression-free survival is associated with overall survival.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to recursive partitioning analysis class (III vs IV vs V), MGMT gene methylation status (methylated vs nonmethylated vs indeterminate), and radiotherapy criteria used (standard vs revised European).
After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1173 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Trial Comparing Conventional Adjuvant Temozolomide With Dose-Intensive Temozolomide in Patients With Newly Diagnosed Glioblastoma
Study Start Date
:
Jan 1, 2006
Actual Primary Completion Date
:
Feb 1, 2011
Actual Study Completion Date
:
Dec 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Conventional adjuvant TMZ Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. |
Drug: Concurrent temozolomide
Daily oral temozolomide (75 mg/m2) up to 49 doses.
Radiation: Concurrent radiation therapy
60 Gy in 2 Gy fractions
Drug: 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle
Oral temozolomide on days 1-5 of a 28-day cycle. Dose starts at 150mg/m2 for first cycle, increases to 200mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.
|
| Experimental: Dose-dense adjuvant TMZ Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
Drug: Concurrent temozolomide
Daily oral temozolomide (75 mg/m2) up to 49 doses.
Radiation: Concurrent radiation therapy
60 Gy in 2 Gy fractions
Drug: 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle
Oral temozolomide on days 1-21 of a 28-day cycle. Dose starts at 75mg/m2 for first cycle, increases to 100mg/m2 for subsequent cycles if no unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive up to 6 more courses of temozolomide.
|
| Other: No adjuvant TMZ (not randomized ) Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. |
Drug: Concurrent temozolomide
Daily oral temozolomide (75 mg/m2) up to 49 doses.
Radiation: Concurrent radiation therapy
60 Gy in 2 Gy fractions
|
Outcome Measures
Primary Outcome Measures
- Median Overall Survival Time [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis occurred after 647 deaths were reported.
Secondary Outcome Measures
- Median Progression-free Survival (PFS) Time [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Analysis occurred after 647 deaths were reported.
- Median Overall Survival Time by MGMT Status [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
- Median Progression-free Survival Time by MGMT Status [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
- Best Treatment Response by MGMT Status [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Response assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.0): Complete Response (CR), imaging no longer shows enhancing tumor, confirmed by a second scan ≥ 4 weeks later; Partial Response (PR), >=50% decrease in tumor area (two diameters) with patient off all steroids, or on adrenal maintenance only; Minor Response (MR), < 50% decrease in tumor area with patient off all steroids, or on adrenal maintenance only; Stable Disease (SD): scan shows no change with patient receiving stable/decreasing doses of steroids; Progression (P): > 25% increase in tumor area with no decrease in steroid dose since last evaluation. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
- Distribution of Highest Grade AE Reported as Possibly/Probably/Definitely Related to Protocol Treatment [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Analysis occurred after 647 deaths were reported.
- Overall Survival Status by Progression Status at 6 Months [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period.
- Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy [Baseline and cycle 10 (approximately 46 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.
- Mean Neurocognitive Function (NCF) Composite Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy [Baseline and cycle 10 (approximately 46 weeks)]
The NCF Composite score is the arithmetic mean of the Hopkins Verbal Learning Test - Revised (HVLT-R) (Free Recall, Delayed Recall, Delayed Recognition), Trail Making Test Part A (TMTA), Trail Making Test Part B (TMTB), and Controlled Oral Word Association (COWA) test scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.
- Mean EORTC QLQ-C30 Global Health Status Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy [Baseline and cycle 10 (approximately 46 weeks)]
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).
- Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 1 [Baseline and mid-cycle 1 (approximately 12 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
- Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 4 [Baseline and mid-cycle 4 (approximately 24 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
- Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 1 [Baseline and mid-cycle 1 (approximately 12 weeks)]
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
- Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 4 [Baseline and mid-cycle 4 (approximately 24 weeks)]
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
- Change From Baseline in Mean EORTC QLQ-C30 Global Health Status [Baseline, 10,12, 22, 24, and 46 weeks]
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline was calculated as time point value - baseline value with a positive change value indicating improved QOL from baseline.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 4 [baseline and cycle 4 (approximately 22 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score at Cycle 4 [baseline and cycle 4 (approximately 22 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (did not interfere) to 10 (interfered completely). The symptom interference score is the average of the symptom interference items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 1 [baseline and cycle 1 (approximately 10 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 4 [baseline and cycle 4 (approximately 22 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 10 [baseline and cycle 10 (approximately 46 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
- Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score Over Time [Baseline, 10, 12, 22, 24, and 46 weeks]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.
- Determination of Impactful Baseline Instruments on Overall Survival [From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.]
Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30 subscales are calculated as the mean of component items, then standardized such that subscale scores range from 0 to 100. A high score for a functional scale represents a healthy level of functioning. Controlled Oral Word Association (COWA) score is the sum of correct responses with a range of 0 to infinity. A higher score indicates better functioning. Hopkins Verbal Learning Test - Revised (HVLT-R) score ranges from 0 to 36 for total recall is 0 to 36, 0 to 12 for delayed recall, and -12 to 12 for recognition. A higher score indicates better functioning.
- Mean Neurocognitive Function (NCF) Composite Score Over Time [Baseline, 10, 22, and 46 weeks]
The NCF Composite score is the arithmetic mean of the HVLT-R (Free Recall, Delayed Recall, Delayed Recognition), TMTA, TMTB, and COWA scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition Score at Cycle 1 [baseline and cycle 1 (approximately 10 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 4 [baseline and cycle 4 (approximately 22 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
- Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 10 [baseline and cycle 10 (approximately 46 weeks)]
The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 120 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
-
Patients must have at least 1 block of tissue available for analysis of MGMT status; fresh frozen tumor tissue acquisition is encouraged.
-
Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible.
-
The tumor must have a supratentorial component.
-
Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration.
-
A diagnostic contrast-enhanced magnetic resonance imaging (MRI) or computerized tomography (CT) scan (if MRI is not available) of the brain must be performed preoperatively and postoperatively. The postoperative scan must be done within 28 days of registration and prior to the initiation of radiotherapy. Preoperative and postoperative scans must be the same type. If CT scans were performed perioperatively, a CT and an MRI should be performed before randomization.
6.1. Patients unable to undergo MRI imaging because of non-compatible devices can be enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and are of sufficient quality.
-
Therapy must begin ≤ 5 weeks after the most recent brain tumor surgery.
-
History/physical examination within 14 days prior to study registration.
-
Neurologic examination within 14 days prior to study registration.
-
Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration.
-
Karnofsky performance status of ≥ 60.
-
Age ≥ 18 years.
-
Complete blood count (CBC)/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined below: 13.1 Absolute neutrophil count (ANC) ≥ 1500 cells/mm3. 13.2 Platelets ≥ 100,000 cells/mm3. 13.3 Hemoglobin ≥ 10 g/dl. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
-
Adequate renal function, as defined below:
14.1 Blood urea nitrogen (BUN) ≤ 25 mg/dl within 14 days prior to study registration 14.2 Creatinine ≤ 1.7 mg/dl within 14 days prior to study registration
- Adequate hepatic function, as defined below:
15.1 Bilirubin ≤ 2.0 mg/dl within 14 days prior to study registration 15.2 Alanine aminotransferase (ALT) ≤ 3 x normal range within 14 days prior to study registration 15.3 Aspartate aminotransferase (AST) ≤ 3 x normal range within 14 days prior to study registration
- Patients must sign a study-specific informed consent prior to study registration.
If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.
-
For females of child-bearing potential, negative serum pregnancy test within 72 hours prior to starting temozolomide.
-
Women of childbearing potential and male participants must practice adequate
Exclusion criteria:
-
Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible).
-
Recurrent or multifocal malignant gliomas
-
Metastases detected below the tentorium or beyond the cranial vault.
-
Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted. See Section 1.
-
Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
-
Severe, active co-morbidity, defined as follows:
-
6.1. Unstable angina and/or congestive heart failure requiring hospitalization.
-
6.2. Transmural myocardial infarction within the last 6 months.
-
6.3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
-
6.4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
-
6.5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
-
6.6. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
-
6.7. Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
-
6.8. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
-
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
-
Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug;
-
Prior allergic reaction to temozolomide.
-
Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
-
No tissue provided for histopathologic central review and MGMT status.
-
Tissue provided by stereotactic biopsy method.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital | Fairbanks | Alaska | United States | 99701 |
| 2 | Arizona Oncology Services Foundation | Phoenix | Arizona | United States | 85013 |
| 3 | Mayo Clinic Scottsdale | Scottsdale | Arizona | United States | 85259-5499 |
| 4 | Arizona Oncology - Tucson | Tucson | Arizona | United States | 85704 |
| 5 | Auburn Radiation Oncology | Auburn | California | United States | 95603 |
| 6 | Providence Saint Joseph Medical Center - Burbank | Burbank | California | United States | 91505 |
| 7 | Radiation Oncology Centers - Cameron Park | Cameron Park | California | United States | 95682 |
| 8 | Mercy Cancer Center at Mercy San Juan Medical Center | Carmichael | California | United States | 95608 |
| 9 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010-3000 |
| 10 | Kaiser Permanente Medical Center - Los Angeles | Los Angeles | California | United States | 90027 |
| 11 | Radiation Oncology Center - Roseville | Roseville | California | United States | 95661 |
| 12 | Radiological Associates of Sacramento Medical Group, Incorporated | Sacramento | California | United States | 95815 |
| 13 | Mercy General Hospital | Sacramento | California | United States | 95819 |
| 14 | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94115 |
| 15 | Solano Radiation Oncology Center | Vacaville | California | United States | 95687 |
| 16 | Penrose Cancer Center at Penrose Hospital | Colorado Springs | Colorado | United States | 80933 |
| 17 | Poudre Valley Radiation Oncology | Fort Collins | Colorado | United States | 80528 |
| 18 | Yale Cancer Center | New Haven | Connecticut | United States | 06520-8028 |
| 19 | Tunnell Cancer Center at Beebe Medical Center | Lewes | Delaware | United States | 19958 |
| 20 | CCOP - Christiana Care Health Services | Newark | Delaware | United States | 19713 |
| 21 | Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus | Boca Raton | Florida | United States | 33486 |
| 22 | University of Florida Shands Cancer Center | Gainesville | Florida | United States | 32610-0232 |
| 23 | Integrated Community Oncology Network | Jacksonville Beach | Florida | United States | 32250 |
| 24 | Baptist Cancer Institute - Jacksonville | Jacksonville | Florida | United States | 32207 |
| 25 | Integrated Community Oncology Network at Southside Cancer Center | Jacksonville | Florida | United States | 32207 |
| 26 | Mayo Clinic - Jacksonville | Jacksonville | Florida | United States | 32224 |
| 27 | Baptist Medical Center South | Jacksonville | Florida | United States | 32258 |
| 28 | Baptist-South Miami Regional Cancer Program | Miami | Florida | United States | 33176 |
| 29 | Integrated Community Oncology Network - Orange Park | Orange Park | Florida | United States | 32073 |
| 30 | Florida Cancer Center - Palatka | Palatka | Florida | United States | 32177 |
| 31 | Flagler Cancer Center | Saint Augustine | Florida | United States | 32086 |
| 32 | H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa | Florida | United States | 33612-9497 |
| 33 | Piedmont Hospital | Atlanta | Georgia | United States | 30309 |
| 34 | John B. Amos Cancer Center | Columbus | Georgia | United States | 31904 |
| 35 | Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center | Boise | Idaho | United States | 83706 |
| 36 | Northwest Community Hospital | Arlington Heights | Illinois | United States | 60005 |
| 37 | Rush-Copley Cancer Care Center | Aurora | Illinois | United States | 60504 |
| 38 | St. Joseph Medical Center | Bloomington | Illinois | United States | 61701 |
| 39 | Graham Hospital | Canton | Illinois | United States | 61520 |
| 40 | Memorial Hospital | Carthage | Illinois | United States | 62321 |
| 41 | John H. Stroger, Jr. Hospital of Cook County | Chicago | Illinois | United States | 60612-3785 |
| 42 | University of Chicago Cancer Research Center | Chicago | Illinois | United States | 60637-1470 |
| 43 | Eureka Community Hospital | Eureka | Illinois | United States | 61530 |
| 44 | Galesburg Clinic, PC | Galesburg | Illinois | United States | 61401 |
| 45 | Galesburg Cottage Hospital | Galesburg | Illinois | United States | 61401 |
| 46 | InterCommunity Cancer Center of Western Illinois | Galesburg | Illinois | United States | 61401 |
| 47 | Mason District Hospital | Havana | Illinois | United States | 62644 |
| 48 | Hopedale Medical Complex | Hopedale | Illinois | United States | 61747 |
| 49 | Joliet Oncology-Hematology Associates, Limited - West | Joliet | Illinois | United States | 60435 |
| 50 | McDonough District Hospital | Macomb | Illinois | United States | 61455 |
| 51 | Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 52 | BroMenn Regional Medical Center | Normal | Illinois | United States | 61761 |
| 53 | Community Cancer Center | Normal | Illinois | United States | 61761 |
| 54 | Community Hospital of Ottawa | Ottawa | Illinois | United States | 61350 |
| 55 | Oncology Hematology Associates of Central Illinois, PC - Ottawa | Ottawa | Illinois | United States | 61350 |
| 56 | Cancer Treatment Center at Pekin Hospital | Pekin | Illinois | United States | 61554 |
| 57 | Proctor Hospital | Peoria | Illinois | United States | 61614 |
| 58 | OSF St. Francis Medical Center | Peoria | Illinois | United States | 61615-7827 |
| 59 | CCOP - Illinois Oncology Research Association | Peoria | Illinois | United States | 61615 |
| 60 | Oncology Hematology Associates of Central Illinois, PC - Peoria | Peoria | Illinois | United States | 61615 |
| 61 | Methodist Medical Center of Illinois | Peoria | Illinois | United States | 61636 |
| 62 | Illinois Valley Community Hospital | Peru | Illinois | United States | 61354 |
| 63 | Perry Memorial Hospital | Princeton | Illinois | United States | 61356 |
| 64 | St. Margaret's Hospital | Spring Valley | Illinois | United States | 61362 |
| 65 | Valley Cancer Center | Spring Valley | Illinois | United States | 61362 |
| 66 | Carle Cancer Center at Carle Foundation Hospital | Urbana | Illinois | United States | 61801 |
| 67 | CCOP - Carle Cancer Center | Urbana | Illinois | United States | 61801 |
| 68 | Elkhart General Hospital | Elkhart | Indiana | United States | 46515 |
| 69 | Radiation Oncology Associates Southwest | Fort Wayne | Indiana | United States | 46804 |
| 70 | Parkview Regional Cancer Center at Parkview Health | Fort Wayne | Indiana | United States | 46805 |
| 71 | Central Indiana Cancer Centers - East | Indianapolis | Indiana | United States | 46219 |
| 72 | Howard Community Hospital | Kokomo | Indiana | United States | 46904 |
| 73 | Center for Cancer Therapy at LaPorte Hospital and Health Services | La Porte | Indiana | United States | 46350 |
| 74 | Saint Anthony Memorial Health Centers | Michigan City | Indiana | United States | 46360 |
| 75 | CCOP - Northern Indiana CR Consortium | South Bend | Indiana | United States | 46601 |
| 76 | Memorial Hospital of South Bend | South Bend | Indiana | United States | 46601 |
| 77 | Saint Joseph Regional Medical Center | South Bend | Indiana | United States | 46617 |
| 78 | South Bend Clinic | South Bend | Indiana | United States | 46617 |
| 79 | McFarland Clinic, PC | Ames | Iowa | United States | 50010 |
| 80 | Mercy Capitol Hospital | Des Moines | Iowa | United States | 50307 |
| 81 | CCOP - Iowa Oncology Research Association | Des Moines | Iowa | United States | 50309 |
| 82 | John Stoddard Cancer Center at Iowa Methodist Medical Center | Des Moines | Iowa | United States | 50309 |
| 83 | Medical Oncology and Hematology Associates at John Stoddard Cancer Center | Des Moines | Iowa | United States | 50309 |
| 84 | Medical Oncology and Hematology Associates at Mercy Cancer Center | Des Moines | Iowa | United States | 50314 |
| 85 | Mercy Cancer Center at Mercy Medical Center - Des Moines | Des Moines | Iowa | United States | 50314 |
| 86 | John Stoddard Cancer Center at Iowa Lutheran Hospital | Des Moines | Iowa | United States | 50316 |
| 87 | Mercy Cancer Center at Mercy Medical Center - North Iowa | Mason City | Iowa | United States | 50401 |
| 88 | Cancer Center of Kansas, PA - Chanute | Chanute | Kansas | United States | 66720 |
| 89 | Cancer Center of Kansas, PA - Dodge City | Dodge City | Kansas | United States | 67801 |
| 90 | Cancer Center of Kansas, PA - El Dorado | El Dorado | Kansas | United States | 67042 |
| 91 | Cancer Center of Kansas-Independence | Independence | Kansas | United States | 67301 |
| 92 | Cancer Center of Kansas, PA - Kingman | Kingman | Kansas | United States | 67068 |
| 93 | Southwest Medical Center | Liberal | Kansas | United States | 67901 |
| 94 | Cancer Center of Kansas, PA - Newton | Newton | Kansas | United States | 67114 |
| 95 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
| 96 | Kansas City Cancer Centers - Southwest | Overland Park | Kansas | United States | 66210 |
| 97 | Cancer Center of Kansas, PA - Parsons | Parsons | Kansas | United States | 67357 |
| 98 | Cancer Center of Kansas, PA - Pratt | Pratt | Kansas | United States | 67124 |
| 99 | Cancer Center of Kansas, PA - Salina | Salina | Kansas | United States | 67042 |
| 100 | Shawnee Mission Medical Center | Shawnee Mission | Kansas | United States | 66204 |
| 101 | Cancer Center of Kansas, PA - Wellington | Wellington | Kansas | United States | 67152 |
| 102 | Associates in Womens Health, PA - North Review | Wichita | Kansas | United States | 67208 |
| 103 | Cancer Center of Kansas, PA - Medical Arts Tower | Wichita | Kansas | United States | 67208 |
| 104 | Cancer Center of Kansas, PA - Wichita | Wichita | Kansas | United States | 67214 |
| 105 | CCOP - Wichita | Wichita | Kansas | United States | 67214 |
| 106 | Via Christi Cancer Center at Via Christi Regional Medical Center | Wichita | Kansas | United States | 67214 |
| 107 | Wesley Medical Center | Wichita | Kansas | United States | 67214 |
| 108 | Cancer Center of Kansas, PA - Winfield | Winfield | Kansas | United States | 67156 |
| 109 | DeCesaris Cancer Institute at Anne Arundel Medical Center | Annapolis | Maryland | United States | 21401 |
| 110 | St. Agnes Hospital Cancer Center | Baltimore | Maryland | United States | 21229 |
| 111 | Union Hospital Cancer Program at Union Hospital | Elkton | Maryland | United States | 21921 |
| 112 | Hickman Cancer Center at Bixby Medical Center | Adrian | Michigan | United States | 49221 |
| 113 | Saint Joseph Mercy Cancer Center | Ann Arbor | Michigan | United States | 48106-0995 |
| 114 | CCOP - Michigan Cancer Research Consortium | Ann Arbor | Michigan | United States | 48106 |
| 115 | Oakwood Cancer Center at Oakwood Hospital and Medical Center | Dearborn | Michigan | United States | 48123-2500 |
| 116 | Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 117 | Green Bay Oncology, Limited - Escanaba | Escanaba | Michigan | United States | 49431 |
| 118 | Genesys Hurley Cancer Institute | Flint | Michigan | United States | 48503 |
| 119 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 120 | Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods | Michigan | United States | 48236 |
| 121 | Dickinson County Healthcare System | Iron Mountain | Michigan | United States | 49801 |
| 122 | Foote Memorial Hospital | Jackson | Michigan | United States | 49201 |
| 123 | Borgess Medical Center | Kalamazoo | Michigan | United States | 49001 |
| 124 | West Michigan Cancer Center | Kalamazoo | Michigan | United States | 49007-3731 |
| 125 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 126 | Haematology-Oncology Associates of Ohio and Michigan, PC | Lambertville | Michigan | United States | 48144 |
| 127 | Sparrow Regional Cancer Center | Lansing | Michigan | United States | 48912-1811 |
| 128 | St. Mary Mercy Hospital | Livonia | Michigan | United States | 48154 |
| 129 | Community Cancer Center of Monroe | Monroe | Michigan | United States | 48162 |
| 130 | Mercy Memorial Hospital - Monroe | Monroe | Michigan | United States | 48162 |
| 131 | St. Joseph Mercy Oakland | Pontiac | Michigan | United States | 48341-2985 |
| 132 | Mercy Regional Cancer Center at Mercy Hospital | Port Huron | Michigan | United States | 48060 |
| 133 | William Beaumont Hospital - Royal Oak Campus | Royal Oak | Michigan | United States | 48073 |
| 134 | Seton Cancer Institute at Saint Mary's - Saginaw | Saginaw | Michigan | United States | 48601 |
| 135 | Lakeland Regional Cancer Care Center - St. Joseph | Saint Joseph | Michigan | United States | 49085 |
| 136 | Providence Cancer Institute at Providence Hospital - Southfield Campus | Southfield | Michigan | United States | 48075 |
| 137 | St. John Macomb Hospital | Warren | Michigan | United States | 48093 |
| 138 | Alexandria | Minnesota | United States | 56308 | |
| 139 | MeritCare Bemidji | Bemidji | Minnesota | United States | 56601 |
| 140 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 141 | Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 142 | Fairview Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 143 | Fergus Falls | Minnesota | United States | 56537 | |
| 144 | Mercy and Unity Cancer Center at Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 145 | Minnesota Oncology Hematology, PA - Maplewood | Maplewood | Minnesota | United States | 55109 |
| 146 | Virginia Piper Cancer Institute at Abbott - Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 147 | Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center | Robbinsdale | Minnesota | United States | 55422-2900 |
| 148 | Mayo Clinic Cancer Center | Rochester | Minnesota | United States | 55905 |
| 149 | CentraCare Clinic - River Campus | Saint Cloud | Minnesota | United States | 56303 |
| 150 | Coborn Cancer Center | Saint Cloud | Minnesota | United States | 56303 |
| 151 | CCOP - Metro-Minnesota | Saint Louis Park | Minnesota | United States | 55416 |
| 152 | Park Nicollet Cancer Center | Saint Louis Park | Minnesota | United States | 55416 |
| 153 | United Hospital | Saint Paul | Minnesota | United States | 55102 |
| 154 | Ridgeview Medical Center | Waconia | Minnesota | United States | 55387 |
| 155 | Minnesota Oncology Hematology, PA - Woodbury | Woodbury | Minnesota | United States | 55125 |
| 156 | Independence Regional Health Center | Independence | Missouri | United States | 64050 |
| 157 | St. John's Regional Medical Center | Joplin | Missouri | United States | 64804 |
| 158 | Truman Medical Center - Hospital Hill | Kansas City | Missouri | United States | 64108 |
| 159 | Saint Luke's Cancer Institute at Saint Luke's Hospital | Kansas City | Missouri | United States | 64111 |
| 160 | St. Joseph Medical Center | Kansas City | Missouri | United States | 64114 |
| 161 | North Kansas City Hospital | Kansas City | Missouri | United States | 64116 |
| 162 | Parvin Radiation Oncology | Kansas City | Missouri | United States | 64116 |
| 163 | CCOP - Kansas City | Kansas City | Missouri | United States | 64131 |
| 164 | Kansas City Cancer Centers - South | Kansas City | Missouri | United States | 64131 |
| 165 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 166 | Liberty Hospital | Liberty | Missouri | United States | 64068 |
| 167 | Heartland Regional Medical Center | Saint Joseph | Missouri | United States | 64506 |
| 168 | CCOP - Cancer Research for the Ozarks | Springfield | Missouri | United States | 65802 |
| 169 | St. John's Regional Health Center | Springfield | Missouri | United States | 65804 |
| 170 | Hulston Cancer Center at Cox Medical Center South | Springfield | Missouri | United States | 65807 |
| 171 | CCOP - Montana Cancer Consortium | Billings | Montana | United States | 59101 |
| 172 | Hematology-Oncology Centers of the Northern Rockies - Billings | Billings | Montana | United States | 59101 |
| 173 | Northern Rockies Radiation Oncology Center | Billings | Montana | United States | 59101 |
| 174 | St. Vincent Healthcare Cancer Care Services | Billings | Montana | United States | 59101 |
| 175 | Billings Clinic - Downtown | Billings | Montana | United States | 59107-7000 |
| 176 | St. James Healthcare Cancer Care | Butte | Montana | United States | 59701 |
| 177 | Great Falls Clinic - Main Facility | Great Falls | Montana | United States | 59405 |
| 178 | Great Falls | Montana | United States | 59405 | |
| 179 | Northern Montana Hospital | Havre | Montana | United States | 59501 |
| 180 | Glacier Oncology, PLLC | Kalispell | Montana | United States | 59901 |
| 181 | Kalispell Medical Oncology at KRMC | Kalispell | Montana | United States | 59901 |
| 182 | Kalispell Regional Medical Center | Kalispell | Montana | United States | 59901 |
| 183 | Community Medical Center | Missoula | Montana | United States | 59801 |
| 184 | Guardian Oncology and Center for Wellness | Missoula | Montana | United States | 59804 |
| 185 | Montana Cancer Specialists at Montana Cancer Center | Missoula | Montana | United States | 59807-7877 |
| 186 | Montana Cancer Center at St. Patrick Hospital and Health Sciences Center | Missoula | Montana | United States | 59807 |
| 187 | Good Samaritan Cancer Center at Good Samaritan Hospital | Kearney | Nebraska | United States | 68848-1990 |
| 188 | Cancer Resource Center - Lincoln | Lincoln | Nebraska | United States | 68510 |
| 189 | CCOP - Missouri Valley Cancer Consortium | Omaha | Nebraska | United States | 68106 |
| 190 | Methodist Estabrook Cancer Center | Omaha | Nebraska | United States | 68114 |
| 191 | Immanuel Medical Center | Omaha | Nebraska | United States | 68122 |
| 192 | Alegant Health Cancer Center at Bergan Mercy Medical Center | Omaha | Nebraska | United States | 68124 |
| 193 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131-2197 |
| 194 | University Medical Center of Southern Nevada | Las Vegas | Nevada | United States | 89102 |
| 195 | CCOP - Nevada Cancer Research Foundation | Las Vegas | Nevada | United States | 89106 |
| 196 | Dartmouth - Hitchcock Concord | Concord | New Hampshire | United States | 03301 |
| 197 | Kingsbury Center for Cancer Care at Cheshire Medical Center | Keene | New Hampshire | United States | 03431 |
| 198 | Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756-0002 |
| 199 | St. Barnabas Medical Center Cancer Center | Livingston | New Jersey | United States | 07039 |
| 200 | Frederick R. and Betty M. Smith Cancer Treatment Center | Sparta | New Jersey | United States | 07871 |
| 201 | Cancer Institute of New Jersey at Cooper - Voorhees | Voorhees | New Jersey | United States | 08043 |
| 202 | New York Methodist Hospital | Brooklyn | New York | United States | 11215 |
| 203 | Monter Cancer Center of the North Shore-LIJ Health System | Lake Success | New York | United States | 11042 |
| 204 | CCOP - North Shore University Hospital | Manhasset | New York | United States | 11030 |
| 205 | Don Monti Comprehensive Cancer Center at North Shore University Hospital | Manhasset | New York | United States | 11030 |
| 206 | Long Island Jewish Medical Center | New Hyde Park | New York | United States | 11040 |
| 207 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 208 | Hudson Valley Oncology Associates | Poughkeepsie | New York | United States | 12601 |
| 209 | Lipson Cancer and Blood Center at Rochester General Hospital | Rochester | New York | United States | 14621 |
| 210 | Mission Hospitals - Memorial Campus | Asheville | North Carolina | United States | 28801 |
| 211 | Wayne Memorial Hospital, Incorporated | Goldsboro | North Carolina | United States | 27534 |
| 212 | Wayne Radiation Oncology | Goldsboro | North Carolina | United States | 27534 |
| 213 | Rutherford Hospital | Rutherfordton | North Carolina | United States | 28139 |
| 214 | Wilmed Radiation Oncology Services | Wilson | North Carolina | United States | 27893 |
| 215 | CCOP - MeritCare Hospital | Fargo | North Dakota | United States | 58122 |
| 216 | MeritCare Broadway | Fargo | North Dakota | United States | 58122 |
| 217 | McDowell Cancer Center at Akron General Medical Center | Akron | Ohio | United States | 44307 |
| 218 | Summa Center for Cancer Care at Akron City Hospital | Akron | Ohio | United States | 44309-2090 |
| 219 | Mary Rutan Hospital | Bellefontaine | Ohio | United States | 43311 |
| 220 | Wood County Oncology Center | Bowling Green | Ohio | United States | 43402 |
| 221 | Aultman Cancer Center at Aultman Hospital | Canton | Ohio | United States | 44710-1799 |
| 222 | Adena Regional Medical Center | Chillicothe | Ohio | United States | 45601 |
| 223 | Cleveland Clinic Cancer Center at Fairview Hospital | Cleveland | Ohio | United States | 44111 |
| 224 | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | United States | 44195 |
| 225 | Riverside Methodist Hospital Cancer Care | Columbus | Ohio | United States | 43214-3998 |
| 226 | CCOP - Columbus | Columbus | Ohio | United States | 43215 |
| 227 | Grant Medical Center Cancer Care | Columbus | Ohio | United States | 43215 |
| 228 | Mount Carmel Health - West Hospital | Columbus | Ohio | United States | 43222 |
| 229 | Doctors Hospital at Ohio Health | Columbus | Ohio | United States | 43228 |
| 230 | Grady Memorial Hospital | Delaware | Ohio | United States | 43015 |
| 231 | Cleveland Clinic Cancer Center | Independence | Ohio | United States | 44131 |
| 232 | Fairfield Medical Center | Lancaster | Ohio | United States | 43130 |
| 233 | Lima Memorial Hospital | Lima | Ohio | United States | 45804 |
| 234 | Strecker Cancer Center at Marietta Memorial Hospital | Marietta | Ohio | United States | 45750 |
| 235 | Northwest Ohio Oncology Center | Maumee | Ohio | United States | 43537 |
| 236 | St. Luke's Hospital | Maumee | Ohio | United States | 43537 |
| 237 | Licking Memorial Cancer Care Program at Licking Memorial Hospital | Newark | Ohio | United States | 43055 |
| 238 | St. Charles Mercy Hospital | Oregon | Ohio | United States | 43616 |
| 239 | Toledo Clinic - Oregon | Oregon | Ohio | United States | 43616 |
| 240 | Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford | Salem | Ohio | United States | 44460 |
| 241 | North Coast Cancer Care, Incorporated | Sandusky | Ohio | United States | 44870 |
| 242 | Mercy Medical Center | Springfield | Ohio | United States | 45504 |
| 243 | Community Hospital of Springfield and Clark County | Springfield | Ohio | United States | 45505 |
| 244 | Flower Hospital Cancer Center | Sylvania | Ohio | United States | 43560 |
| 245 | Mercy Hospital of Tiffin | Tiffin | Ohio | United States | 44883 |
| 246 | Toledo Hospital | Toledo | Ohio | United States | 43606 |
| 247 | St. Vincent Mercy Medical Center | Toledo | Ohio | United States | 43608 |
| 248 | Medical University of Ohio Cancer Center | Toledo | Ohio | United States | 43614 |
| 249 | CCOP - Toledo Community Hospital | Toledo | Ohio | United States | 43617 |
| 250 | Toledo Clinic, Incorporated - Main Clinic | Toledo | Ohio | United States | 43623 |
| 251 | Fulton County Health Center | Wauseon | Ohio | United States | 43567 |
| 252 | Mount Carmel St. Ann's Cancer Center | Westerville | Ohio | United States | 43081 |
| 253 | Cancer Treatment Center | Wooster | Ohio | United States | 44691 |
| 254 | Genesis - Good Samaritan Hospital | Zanesville | Ohio | United States | 43701 |
| 255 | Oklahoma University Cancer Institute | Oklahoma City | Oklahoma | United States | 73104 |
| 256 | Natalie Warren Bryant Cancer Center at St. Francis Hospital | Tulsa | Oklahoma | United States | 74136 |
| 257 | Willamette Valley Cancer Center - Eugene | Eugene | Oregon | United States | 97401 |
| 258 | Legacy Mount Hood Medical Center | Gresham | Oregon | United States | 97030 |
| 259 | Providence Milwaukie Hospital | Milwaukie | Oregon | United States | 97222 |
| 260 | Legacy Good Samaritan Hospital & Comprehensive Cancer Center | Portland | Oregon | United States | 97210 |
| 261 | Providence Cancer Center at Providence Portland Medical Center | Portland | Oregon | United States | 97213-2967 |
| 262 | Adventist Medical Center | Portland | Oregon | United States | 97216 |
| 263 | CCOP - Columbia River Oncology Program | Portland | Oregon | United States | 97225 |
| 264 | Providence St. Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 265 | Legacy Emanuel Hospital and Health Center and Children's Hospital | Portland | Oregon | United States | 97227 |
| 266 | Salem Hospital Regional Cancer Care Services | Salem | Oregon | United States | 97309-5014 |
| 267 | Legacy Meridian Park Hospital | Tualatin | Oregon | United States | 97062 |
| 268 | Rosenfeld Cancer Center at Abington Memorial Hospital | Abington | Pennsylvania | United States | 19001 |
| 269 | Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest | Allentown | Pennsylvania | United States | 18105 |
| 270 | Bryn Mawr Hospital | Bryn Mawr | Pennsylvania | United States | 19010 |
| 271 | Geisinger Cancer Institute at Geisinger Health | Danville | Pennsylvania | United States | 17822-0001 |
| 272 | Northeast Radiation Oncology Center | Dunmore | Pennsylvania | United States | 18512 |
| 273 | Dale and Frances Hughes Cancer Center at Pocono Medical Center | East Stroudsburg | Pennsylvania | United States | 18301 |
| 274 | Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey | Pennsylvania | United States | 17033-0850 |
| 275 | Riddle Memorial Hospital Cancer Center | Media | Pennsylvania | United States | 19063 |
| 276 | Upper Delaware Valley Cancer Center | Milford | Pennsylvania | United States | 18337 |
| 277 | Intercommunity Cancer Center | Monroeville | Pennsylvania | United States | 15146 |
| 278 | Alle-Kiski Medical Center | Natrona Heights | Pennsylvania | United States | 15065 |
| 279 | Cancer Center of Paoli Memorial Hospital | Paoli | Pennsylvania | United States | 19301-1792 |
| 280 | Kimmel Cancer Center at Thomas Jefferson University - Philadelphia | Philadelphia | Pennsylvania | United States | 19107-5541 |
| 281 | Fox Chase Cancer Center - Philadelphia | Philadelphia | Pennsylvania | United States | 19111-2497 |
| 282 | Frankford Hospital Cancer Center - Torresdale Campus | Philadelphia | Pennsylvania | United States | 19114 |
| 283 | Allegheny Cancer Center at Allegheny General Hospital | Pittsburgh | Pennsylvania | United States | 15212 |
| 284 | McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center | Reading | Pennsylvania | United States | 19612-6052 |
| 285 | Somerset Oncology Center | Somerset | Pennsylvania | United States | 15501 |
| 286 | Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center | Wilkes-Barre | Pennsylvania | United States | 18711 |
| 287 | CCOP - Main Line Health | Wynnewood | Pennsylvania | United States | 19096 |
| 288 | Lankenau Cancer Center at Lankenau Hospital | Wynnewood | Pennsylvania | United States | 19096 |
| 289 | AnMed Cancer Center | Anderson | South Carolina | United States | 29621 |
| 290 | Hollings Cancer Center at Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 291 | CCOP - Upstate Carolina | Spartanburg | South Carolina | United States | 29303 |
| 292 | Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg | South Carolina | United States | 29303 |
| 293 | Rapid City Regional Hospital | Rapid City | South Dakota | United States | 57701 |
| 294 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 295 | Medical X-Ray Center, PC | Sioux Falls | South Dakota | United States | 57105 |
| 296 | Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls | South Dakota | United States | 57117-5039 |
| 297 | Thompson Cancer Survival Center West | Knoxville | Tennessee | United States | 37392 |
| 298 | Thompson Cancer Survival Center | Knoxville | Tennessee | United States | 37916 |
| 299 | Thompson Cancer Survival Center at Methodist | Oak Ridge | Tennessee | United States | 37830 |
| 300 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 301 | Texas Oncology, PA at Texas Cancer Center Dallas Southwest | Dallas | Texas | United States | 75237 |
| 302 | Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital | Fort Worth | Texas | United States | 76104 |
| 303 | M. D. Anderson Cancer Center at University of Texas | Houston | Texas | United States | 77030-4009 |
| 304 | Joe Arrington Cancer Research and Treatment Center | Lubbock | Texas | United States | 79410-1894 |
| 305 | Texas Oncology, PA at Texas Cancer Center - Sherman | Sherman | Texas | United States | 75090 |
| 306 | Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land | Sugar Land | Texas | United States | 77479 |
| 307 | American Fork Hospital | American Fork | Utah | United States | 84003 |
| 308 | Sandra L. Maxwell Cancer Center | Cedar City | Utah | United States | 84720 |
| 309 | Jon and Karen Huntsman Cancer Center at Intermountain Medical Center | Murray | Utah | United States | 84157 |
| 310 | Val and Ann Browning Cancer Center at McKay-Dee Hospital Center | Ogden | Utah | United States | 84403 |
| 311 | Utah Valley Regional Medical Center - Provo | Provo | Utah | United States | 84604 |
| 312 | Dixie Regional Medical Center - East Campus | Saint George | Utah | United States | 84770 |
| 313 | LDS Hospital | Salt Lake City | Utah | United States | 84103 |
| 314 | Utah Cancer Specialists at UCS Cancer Center | Salt Lake City | Utah | United States | 84106 |
| 315 | Huntsman Cancer Institute at University of Utah | Salt Lake City | Utah | United States | 84112 |
| 316 | Fletcher Allen Health Care - University Health Center Campus | Burlington | Vermont | United States | 05401 |
| 317 | Norris Cotton Cancer Center - North | Saint Johnsbury | Vermont | United States | 05819 |
| 318 | Fredericksburg Oncology, Incorporated | Fredericksburg | Virginia | United States | 22401 |
| 319 | Sentara Cancer Institute at Sentara Norfolk General Hospital | Norfolk | Virginia | United States | 23507 |
| 320 | Virginia Commonwealth University Massey Cancer Center | Richmond | Virginia | United States | 23298-0037 |
| 321 | St. Joseph Cancer Center | Bellingham | Washington | United States | 98225 |
| 322 | St. Francis Hospital | Federal Way | Washington | United States | 98003 |
| 323 | Cascade Cancer Center at Evergreen Hospital Medical Center | Kirkland | Washington | United States | 98033 |
| 324 | CCOP - Virginia Mason Research Center | Seattle | Washington | United States | 98101 |
| 325 | University Cancer Center at University of Washington Medical Center | Seattle | Washington | United States | 98195-6043 |
| 326 | Southwest Washington Medical Center Cancer Center | Vancouver | Washington | United States | 98668 |
| 327 | North Star Lodge Cancer Center at Yakima Valley Memorial Hospital | Yakima | Washington | United States | 98902 |
| 328 | Theda Care Cancer Institute | Appleton | Wisconsin | United States | 54911 |
| 329 | Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54301-3526 |
| 330 | Green Bay Oncology, Limited at St. Mary's Hospital | Green Bay | Wisconsin | United States | 54303 |
| 331 | St. Mary's Hospital Medical Center - Green Bay | Green Bay | Wisconsin | United States | 54303 |
| 332 | St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54307-3508 |
| 333 | Gundersen Lutheran Center for Cancer and Blood | La Crosse | Wisconsin | United States | 54601 |
| 334 | University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison | Wisconsin | United States | 53792-6164 |
| 335 | Bay Area Cancer Care Center at Bay Area Medical Center | Marinette | Wisconsin | United States | 54143 |
| 336 | Community Memorial Hospital Cancer Care Center | Menomonee Falls | Wisconsin | United States | 53051 |
| 337 | Regional Cancer Center at Oconomowoc Memorial Hospital | Oconomowoc | Wisconsin | United States | 53066 |
| 338 | Green Bay Oncology, Limited - Oconto Falls | Oconto Falls | Wisconsin | United States | 54154 |
| 339 | Door County Cancer Center at Door County Memorial Hospital | Sturgeon Bay | Wisconsin | United States | 54235-1495 |
| 340 | Green Bay Oncology, Limited - Sturgeon Bay | Sturgeon Bay | Wisconsin | United States | 54235 |
| 341 | Waukesha Memorial Hospital Regional Cancer Center | Waukesha | Wisconsin | United States | 53188 |
| 342 | Tom Baker Cancer Centre - Calgary | Calgary | Alberta | Canada | T2N 4N2 |
| 343 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 344 | Saint John Regional Hospital | Saint John | New Brunswick | Canada | E2L 4L2 |
| 345 | Margaret and Charles Juravinski Cancer Centre | Hamilton | Ontario | Canada | L8V 5C2 |
| 346 | Ottawa Hospital Regional Cancer Centre - General Campus | Ottawa | Ontario | Canada | K1Y 4K7 |
| 347 | Cancer Care Program at Thunder Bay Regional Health Sciences | Thunder Bay | Ontario | Canada | P7B 6V4 |
| 348 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 349 | McGill Cancer Centre at McGill University | Montreal | Quebec | Canada | H2W 1S6 |
| 350 | Centre Hospitalier Universitaire de Quebec | Quebec City | Quebec | Canada | G1R 2J6 |
| 351 | Allan Blair Cancer Centre at Pasqua Hospital | Regina | Saskatchewan | Canada | S4T 7T1 |
Sponsors and Collaborators
- Radiation Therapy Oncology Group
- National Cancer Institute (NCI)
- European Organisation for Research and Treatment of Cancer - EORTC
- NRG Oncology
Investigators
- Principal Investigator: Mark R. Gilbert, MD, M.D. Anderson Cancer Center
- Study Chair: Minesh P. Mehta, MD, University of Wisconsin, Madison
- Study Chair: Roger Stupp, MD, Centre Hospitalier Universitaire Vaudois
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00304031
Other Study ID Numbers:
- RTOG-0525
- CDR0000465183
- EORTC-26052
- EORTC-22053
- NCI-2009-00731
First Posted:
Mar 17, 2006
Last Update Posted:
Jun 9, 2020
Last Verified:
May 1, 2020
Keywords provided by Radiation Therapy Oncology Group
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Sites were required to submit participant tumor tissue for central histologic review and MGMT (O-6-methylguanine-DNA methyltransferase) status determination in order for registered participants to continue on the study. Of 1173 participants initially registered, 1125 participants met these requirements and started protocol treatment. |
| Arm/Group Title | No Adjuvant TMZ (Not Randomized) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|---|
| Arm/Group Description | Concurrent radiation therapy (RT) with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Period Title: Concomitant RT+TMZ (Pre-randomization) | |||
| STARTED | 1125 | 0 | 0 |
| Eligible Pre-randomization Population | 1125 | 0 | 0 |
| Eligible Pre-randomization Follow-up | 1120 | 0 | 0 |
| COMPLETED | 833 | 0 | 0 |
| NOT COMPLETED | 292 | 0 | 0 |
| Period Title: Concomitant RT+TMZ (Pre-randomization) | |||
| STARTED | 0 | 411 | 422 |
| Eligible Population | 0 | 411 | 420 |
| Unmethylated MGMT Population | 0 | 254 | 262 |
| Methylated MGMT Population | 0 | 122 | 122 |
| Quality of Life Population | 0 | 96 | 95 |
| COMPLETED | 0 | 411 | 420 |
| NOT COMPLETED | 0 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | No Adjuvant TMZ (Not Randomized ) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ | Total |
|---|---|---|---|---|
| Arm/Group Description | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. | Total of all reporting groups |
| Overall Participants | 292 | 411 | 422 | 1125 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
60.5
|
57
|
58
|
58
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
126
43.2%
|
172
41.8%
|
185
43.8%
|
483
42.9%
|
| Male |
166
56.8%
|
239
58.2%
|
237
56.2%
|
642
57.1%
|
Outcome Measures
| Title | Median Overall Survival Time |
|---|---|
| Description | Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized eligible patients. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Measure Participants | 411 | 420 |
| Median (95% Confidence Interval) [months] |
16.6
|
14.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | This study was looking for a 20% reduction in hazard rate: null hypothesis (conventional arm): Median survival time (MST) = 14.0 mo.; alternative hypothesis (dose-dense arm): MST= 17.5 mo. A one-sided log-rank test at a significance level of 0.025 would have 80% power to detect this difference with a sample size of 750 patients (647 deaths were required for the final analysis). | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.63 |
| Comments | One-sided | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.88 to 1.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
| Title | Median Progression-free Survival (PFS) Time |
|---|---|
| Description | Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized eligible patients |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Measure Participants | 411 | 420 |
| Median (95% Confidence Interval) [months] |
5.5
|
6.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.06 |
| Comments | Two-side significance level = 0.05 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
| Title | Median Overall Survival Time by MGMT Status |
|---|---|
| Description | Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| MGMT status was not available for all randomized eligible participants. Therefore, data was only available from 376/411 on the conventional arm and 384/420 on the dose-dense arm. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Measure Participants | 376 | 384 |
| Unmethylated MGMT |
14.6
|
13.3
|
| Methylated MGMT |
21.4
|
20.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | Unmethylated MGMT | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.44 |
| Comments | One-sided significance level = 0.05 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.99 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | Methylated MGMT | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.86 |
| Comments | One-sided significance level = 0.05 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.19 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
| Title | Median Progression-free Survival Time by MGMT Status |
|---|---|
| Description | Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| MGMT status was not available for all randomized eligible participants. Therefore, data was only available from 376/411 on the conventional arm and 384/420 on the dose-dense arm. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Measure Participants | 376 | 384 |
| Unmethylated MGMT |
5.1
|
6.0
|
| Methylated MGMT |
6.5
|
10.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | Unmethylated MGMT | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.15 |
| Comments | One-sided significance level = 0.05 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.73 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | Methylated MGMT | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.33 |
| Comments | One-sided significance level = 0.05 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 1.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Reference level = Conventional adjuvant TMZ | |
| Title | Best Treatment Response by MGMT Status |
|---|---|
| Description | Response assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.0): Complete Response (CR), imaging no longer shows enhancing tumor, confirmed by a second scan ≥ 4 weeks later; Partial Response (PR), >=50% decrease in tumor area (two diameters) with patient off all steroids, or on adrenal maintenance only; Minor Response (MR), < 50% decrease in tumor area with patient off all steroids, or on adrenal maintenance only; Stable Disease (SD): scan shows no change with patient receiving stable/decreasing doses of steroids; Progression (P): > 25% increase in tumor area with no decrease in steroid dose since last evaluation. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per the protocol, both arms are combined to compare between MGMT status. MGMT status and treatment response was not available for all randomized eligible participants. Therefore, data was only available for 748/831 randomized eligible patients (arms combined). |
| Arm/Group Title | Methylated | Unmethylated |
|---|---|---|
| Arm/Group Description | Methylated MGMT (O[6]-methylguanine-DNA methyltransferase) | Unmethylated MGMT (O[6]-methylguanine-DNA methyltransferase) |
| Measure Participants | 240 | 508 |
| Complete Response |
47
16.1%
|
67
16.3%
|
| Partial Response |
34
11.6%
|
66
16.1%
|
| Minor Response |
31
10.6%
|
55
13.4%
|
| Stable Response |
110
37.7%
|
243
59.1%
|
| Progressive Disease |
18
6.2%
|
77
18.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | Two-sided significance level of 0.05 | |
| Method | Chi-squared | |
| Comments | ||
| Title | Distribution of Highest Grade AE Reported as Possibly/Probably/Definitely Related to Protocol Treatment |
|---|---|
| Description | Highest grade adverse event (AE) per subject was counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Analysis occurred after 647 deaths were reported. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized eligible patients with any adverse events reported as possibly/probably/definitely related to protocol treatment |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. |
| Measure Participants | 351 | 369 |
| Grade 0,1,2 |
231
79.1%
|
175
42.6%
|
| Grade 3,4,5 |
120
41.1%
|
194
47.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Two-sided significance level of 0.05 | |
| Title | Overall Survival Status by Progression Status at 6 Months |
|---|---|
| Description | Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per the protocol, both arms are combined to compare between 6-month progression status. Eligible pre-randomization participants with any follow-up data. |
| Arm/Group Title | No Progression at 6 Months | Progression at 6 Months |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 676 | 444 |
| Median (95% Confidence Interval) [months] |
20.7
|
10.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Two-sided test | |
| Method | Log Rank | |
| Comments | ||
| Title | Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. |
| Time Frame | Baseline and cycle 10 (approximately 46 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cycle 10 questionnaires were not completed by all quality of life (QOL) population participants progression-free at 6 months. Therefore, only 24/96 on the conventional arm and 20/95 on the dose-dense arm had data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 24 | 20 |
| Mean (95% Confidence Interval) [score on a scale] |
1.17
|
1.18
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.96 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Neurocognitive Function (NCF) Composite Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy |
|---|---|
| Description | The NCF Composite score is the arithmetic mean of the Hopkins Verbal Learning Test - Revised (HVLT-R) (Free Recall, Delayed Recall, Delayed Recognition), Trail Making Test Part A (TMTA), Trail Making Test Part B (TMTB), and Controlled Oral Word Association (COWA) test scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function. |
| Time Frame | Baseline and cycle 10 (approximately 46 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cycle 10 questionnaires were not completed by all QOL population participants progression-free at 6 months. Therefore, only 17/96 on the conventional arm and 20/95 on the dose-dense arm had data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 17 | 20 |
| Mean (95% Confidence Interval) [score on a scale] |
-0.95
|
-1.19
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.73 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean EORTC QLQ-C30 Global Health Status Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy |
|---|---|
| Description | Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). |
| Time Frame | Baseline and cycle 10 (approximately 46 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cycle 10 questionnaires were not completed by all QOL population participants progression-free at 6 months. Therefore, only 24/96 on the conventional arm and 22/95 on the dose-dense arm had data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 24 | 22 |
| Mean (95% Confidence Interval) [score on a scale] |
73.3
|
69.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.57 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 1 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. |
| Time Frame | Baseline and mid-cycle 1 (approximately 12 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 41/96 on the conventional arm and 35/95 on the dose-dense arm have both baseline and mid-cycle 1 data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 41 | 35 |
| Mean (95% Confidence Interval) [score on a scale] |
0.48
|
0.39
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.78 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 4 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. |
| Time Frame | Baseline and mid-cycle 4 (approximately 24 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 32/96 on the conventional arm and 24/95 on the dose-dense arm have both baseline and mid-cycle 4 data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 32 | 24 |
| Mean (95% Confidence Interval) [score on a scale] |
-0.23
|
0.19
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.24 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 1 |
|---|---|
| Description | Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. |
| Time Frame | Baseline and mid-cycle 1 (approximately 12 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 40/96 on the conventional arm and 38/95 on the dose-dense arm have both baseline and mid-cycle 1 data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 40 | 38 |
| Mean (95% Confidence Interval) [score on a scale] |
-4.58
|
-2.63
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.74 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 4 |
|---|---|
| Description | Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline. |
| Time Frame | Baseline and mid-cycle 4 (approximately 24 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 30/96 on the conventional arm and 23/95 on the dose-dense arm have both baseline and mid-cycle 4 data. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 30 | 23 |
| Mean (95% Confidence Interval) [score on a scale] |
-2.78
|
-0.72
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.79 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Change From Baseline in Mean EORTC QLQ-C30 Global Health Status |
|---|---|
| Description | Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline was calculated as time point value - baseline value with a positive change value indicating improved QOL from baseline. |
| Time Frame | Baseline, 10,12, 22, 24, and 46 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with the relevant questions answered at baseline and the given time point on each arm. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 96 | 95 |
| Week 10 (Cycle 1) |
0.0
|
-2.9
|
| Week 12 (Cycle 1.5) |
-4.6
|
-2.7
|
| Week 22 (Cycle 4) |
3.9
|
-4.4
|
| Week 24 (Cycle 4.5) |
-2.8
|
-0.7
|
| Week 46 (Cycle 10) |
5.4
|
-1.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2184 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, RPA class, MGMT status, and time were included in the model. RPA class is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0763 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, RPA class, MGMT status, and time were included in the model. MGMT status is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5235 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 4 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. |
| Time Frame | baseline and cycle 4 (approximately 22 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 51/96 on the conventional arm and 40/95 on the dose-dense arm have both baseline and cycle 4 data |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 51 | 40 |
| Count of Participants [Participants] |
5
1.7%
|
11
2.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | ||
| Method | Z-test of two proportions | |
| Comments | ||
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score at Cycle 4 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (did not interfere) to 10 (interfered completely). The symptom interference score is the average of the symptom interference items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. |
| Time Frame | baseline and cycle 4 (approximately 22 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, only 51/96 on the conventional arm and 40/95 on the dose-dense arm have both baseline and cycle 4 data |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 51 | 40 |
| Count of Participants [Participants] |
7
2.4%
|
13
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | ||
| Method | Z-test of two proportions | |
| Comments | ||
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 1 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows. |
| Time Frame | baseline and cycle 1 (approximately 10 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per the protocol, both arms are combined. Questionnaires were not completed by all QOL population participants. Therefore, only 136/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 1. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 136 |
| Symptom Severity and GHS deterioration |
18
6.2%
|
| Symptom Severity deterioration only |
9
3.1%
|
| GHS deterioratoin only |
31
10.6%
|
| No deterioration |
78
26.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Two-sided test | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 4 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows. |
| Time Frame | baseline and cycle 4 (approximately 22 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires were not completed by all QOL population participants. Therefore, only 86/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 4. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 86 |
| Symptom Severity and GHS deterioration |
10
3.4%
|
| Symptom Severity deterioration only |
5
1.7%
|
| GHS deterioration Only |
18
6.2%
|
| No deterioration |
53
18.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Two-sided test | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 10 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration. The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows. |
| Time Frame | baseline and cycle 10 (approximately 46 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires were not completed by all QOL population participants. Therefore, only 44/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 10. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 44 |
| Symptom Severity and GHS deterioration |
5
1.7%
|
| Symptom Severity deterioration only |
4
1.4%
|
| GHS deterioration only |
5
1.7%
|
| No deterioration |
30
10.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.018 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Two-sided test | |
| Title | Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score Over Time |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. |
| Time Frame | Baseline, 10, 12, 22, 24, and 46 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with the relevant questions answered at baseline and the given time point on each arm. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 95 | 96 |
| Baseline |
1.3
|
1.1
|
| Week 10 (Cycle 1) |
1.4
|
1.4
|
| Week 12 (Cycle 1.5) |
1.6
|
1.5
|
| Week 22 (Cycle 4) |
1.0
|
1.2
|
| Week 24 (Cycle 4.5) |
1.0
|
1.1
|
| Week 46 (Cycle 10) |
1.2
|
1.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with MDASI Symptom Severity Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
| Statistical Test of Hypothesis | p-Value | 0.1702 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. RPA is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8159 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. MGMT status is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2174 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
| Title | Determination of Impactful Baseline Instruments on Overall Survival |
|---|---|
| Description | Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30 subscales are calculated as the mean of component items, then standardized such that subscale scores range from 0 to 100. A high score for a functional scale represents a healthy level of functioning. Controlled Oral Word Association (COWA) score is the sum of correct responses with a range of 0 to infinity. A higher score indicates better functioning. Hopkins Verbal Learning Test - Revised (HVLT-R) score ranges from 0 to 36 for total recall is 0 to 36, 0 to 12 for delayed recall, and -12 to 12 for recognition. A higher score indicates better functioning. |
| Time Frame | From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 154/191 have COWA, EORTC QLQ-C30, and HVLT-R baseline assessments (final model covariates) |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 154 |
| Median (95% Confidence Interval) [months] |
17.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. EORTC physical functioning is reported here. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.023 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. Standardized HVLT-R recognition is reported here. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.043 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. Standardized COWA is reported here. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.021 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Title | Mean Neurocognitive Function (NCF) Composite Score Over Time |
|---|---|
| Description | The NCF Composite score is the arithmetic mean of the HVLT-R (Free Recall, Delayed Recall, Delayed Recognition), TMTA, TMTB, and COWA scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function. |
| Time Frame | Baseline, 10, 22, and 46 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with data at baseline and the given time point on each arm. |
| Arm/Group Title | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ |
|---|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles. |
| Measure Participants | 96 | 95 |
| Baseline |
-1.2
|
-1.5
|
| Week 10 (Cycle 1) |
-1.3
|
-1.45
|
| Week 22 (Cycle 4) |
-1.1
|
-1.3
|
| Week 46 (Cycle 10) |
-1.0
|
-1.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2357 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. RPA is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0147 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ |
|---|---|---|
| Comments | A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. MGMT Status is reported here. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | Each explanatory variable is reported separately. (Time and intercept effects are not shown.) | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition Score at Cycle 1 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows. |
| Time Frame | baseline and cycle 1 (approximately 10 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 116/191 have both MDASI-BT and HVLT-R at baseline and cycle 1. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 116 |
| Cognitive and HVLT-R deterioration |
10
3.4%
|
| Cognitive deterioration only |
12
4.1%
|
| HVLT-R deterioration only |
20
6.8%
|
| No deterioration |
74
25.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.02 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Two-sided test | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 4 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows. |
| Time Frame | baseline and cycle 4 (approximately 22 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 71/191 have both MDASI-BT and HVLT-R at baseline and cycle 4. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 71 |
| Cognitive and Delayed Recognition deterioration |
3
1%
|
| Cognitive deterioration only |
9
3.1%
|
| Delayed Recognition deterioration only |
14
4.8%
|
| No deterioration |
45
15.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.99 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Two-sided test | |
| Title | Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 10 |
|---|---|
| Description | The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration. The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows. |
| Time Frame | baseline and cycle 10 (approximately 46 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 36/191 have both MDASI-BT and HVLT-R at baseline and cycle 10. |
| Arm/Group Title | Both Arms Combined |
|---|---|
| Arm/Group Description | Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles. |
| Measure Participants | 36 |
| Cognitive and Delayed Recognition deterioration |
3
1%
|
| Cognitive deterioration only |
6
2.1%
|
| Delayed Recognition deterioration only |
4
1.4%
|
| No deterioration |
23
7.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Conventional Adjuvant TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.33 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | Two-sided test | |
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Eligible participants with adverse event data: concurrent RT and TMZ only arm (not randomized): 285/292; conventional adjuvant TMZ arm: 409/411; dose-dense adjuvant TMZ arm: 420/422. | |||||
| Arm/Group Title | No Adjuvant TMZ (Not Randomized) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ | |||
| Arm/Group Description | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. | Concurrent radiation therapy with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. | Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. | |||
All Cause Mortality |
||||||
| No Adjuvant TMZ (Not Randomized) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| No Adjuvant TMZ (Not Randomized) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 105/285 (36.8%) | 131/409 (32%) | 142/420 (33.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Blood/bone marrow - Other: | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Bone marrow depression NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Febrile neutropenia | 2/285 (0.7%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Haemolysis NOS | 1/285 (0.4%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Hemoglobin | 12/285 (4.2%) | 6/409 (1.5%) | 5/420 (1.2%) | |||
| Thrombotic microangiopathy NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/285 (0.4%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Atrial flutter | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Atrial tachycardia | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Cardiac General - Other: | 2/285 (0.7%) | 0/409 (0%) | 0/420 (0%) | |||
| Myocardial ischaemia | 1/285 (0.4%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Pericardial effusion | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Sinus bradycardia | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Sinus tachycardia | 1/285 (0.4%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Supraventricular extrasystoles | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Endocrine disorders | ||||||
| Cushingoid | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Hypothyroidism | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Eye disorders | ||||||
| Diplopia | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Extraocular muscle disorder | 0/285 (0%) | 2/409 (0.5%) | 0/420 (0%) | |||
| Ocular/visual - Other: | 0/285 (0%) | 2/409 (0.5%) | 0/420 (0%) | |||
| Photopsia | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Retinal detachment | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Vision blurred | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain NOS | 0/285 (0%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Colitis NOS | 2/285 (0.7%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Colonic perforation | 1/285 (0.4%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Constipation | 0/285 (0%) | 4/409 (1%) | 0/420 (0%) | |||
| Diarrhoea NOS | 1/285 (0.4%) | 2/409 (0.5%) | 3/420 (0.7%) | |||
| Dysphagia | 2/285 (0.7%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Enteritis | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Gastritis NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Gastrointestinal - Other: | 1/285 (0.4%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Nausea | 6/285 (2.1%) | 7/409 (1.7%) | 11/420 (2.6%) | |||
| Oseophagitis NOS | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Pancreatitis NOS | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Rectal hemorrhage | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Small intestinal stricture NOS | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Vomiting NOS | 5/285 (1.8%) | 5/409 (1.2%) | 9/420 (2.1%) | |||
| General disorders | ||||||
| Chest pain | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Constitutional Symptoms - Other: | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Death NOS | 2/285 (0.7%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Disease progression NOS | 6/285 (2.1%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Edema: head and neck: | 0/285 (0%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Edema: limb: | 2/285 (0.7%) | 2/409 (0.5%) | 0/420 (0%) | |||
| Fatigue | 9/285 (3.2%) | 9/409 (2.2%) | 11/420 (2.6%) | |||
| Gait abnormal NOS | 2/285 (0.7%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Influenza-like illness | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Multi-organ failure | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Pain - Other: | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Pain NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Pyrexia | 6/285 (2.1%) | 5/409 (1.2%) | 7/420 (1.7%) | |||
| Rigors | 1/285 (0.4%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Sudden death | 2/285 (0.7%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis NOS | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Hepatic failure | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Immune system disorders | ||||||
| Allergy/immunology - Other: | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Cytokine release syndrome | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Hypersensitivity NOS | 3/285 (1.1%) | 0/409 (0%) | 3/420 (0.7%) | |||
| Infections and infestations | ||||||
| Abdominal infection | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Arthritis infective NOS | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Bladder infection NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Bone infection NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Bronchitis NOS | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Encephalitis NOS | 1/285 (0.4%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Eye infection NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Infection - Other: | 3/285 (1.1%) | 4/409 (1%) | 2/420 (0.5%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Biliary tree | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bladder (urinary) | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bronchus | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Kidney | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Lung (pneumonia) | 1/285 (0.4%) | 2/409 (0.5%) | 4/420 (1%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Meninges (meningitis) | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Rectum | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Soft tissue NOS | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with normal ANC or Grade 1 or 2 neutrophils: Blood | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with normal ANC or Grade 1 or 2 neutrophils: Esophagus | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with normal ANC or Grade 1 or 2 neutrophils: Nerve-peripheral | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Infection with normal ANC or Grade 1 or 2 neutrophils: Wound | 2/285 (0.7%) | 2/409 (0.5%) | 0/420 (0%) | |||
| Infection with unknown ANC: Lung (pneumonia) | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Infection with unknown ANC: Meninges (meningitis) | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Infection with unknown ANC: Skin (cellulitis) | 1/285 (0.4%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Infectous meningitis | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Opportunisitic infection | 1/285 (0.4%) | 0/409 (0%) | 5/420 (1.2%) | |||
| Pneumonia NOS | 0/285 (0%) | 4/409 (1%) | 3/420 (0.7%) | |||
| Respiratory tract infection NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Rhinitis infective | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Sepsis NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Sinusitis NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Skin infection | 1/285 (0.4%) | 5/409 (1.2%) | 1/420 (0.2%) | |||
| Urinary tract infection NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Wound infection | 0/285 (0%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fracture NOS | 2/285 (0.7%) | 1/409 (0.2%) | 3/420 (0.7%) | |||
| Vascular access NOS complication | 2/285 (0.7%) | 3/409 (0.7%) | 1/420 (0.2%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 5/285 (1.8%) | 3/409 (0.7%) | 3/420 (0.7%) | |||
| Aspartate aminotransferase increased | 4/285 (1.4%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Blood alkaline phosphatase increased | 2/285 (0.7%) | 3/409 (0.7%) | 3/420 (0.7%) | |||
| Blood amylase increased | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Blood bilirubin increased | 4/285 (1.4%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Blood creatinine increased | 2/285 (0.7%) | 0/409 (0%) | 2/420 (0.5%) | |||
| CD4 lymphocytes decreased | 0/285 (0%) | 0/409 (0%) | 6/420 (1.4%) | |||
| Gamma-glutamyltransferase increased | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Inappropriate antidiuretic hormone secretion | 1/285 (0.4%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Leukopenia NOS | 17/285 (6%) | 15/409 (3.7%) | 14/420 (3.3%) | |||
| Lipase increased | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Lymphopenia | 11/285 (3.9%) | 5/409 (1.2%) | 23/420 (5.5%) | |||
| Metabolic/laboratory - Other: | 1/285 (0.4%) | 3/409 (0.7%) | 1/420 (0.2%) | |||
| Neutrophil count | 20/285 (7%) | 15/409 (3.7%) | 11/420 (2.6%) | |||
| Platelet count decreased | 34/285 (11.9%) | 20/409 (4.9%) | 16/420 (3.8%) | |||
| Prothrombin time prolonged | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Troponin I increased | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Weight decreased | 1/285 (0.4%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Metabolism and nutrition disorders | ||||||
| Acidosis NOS | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Alkalosis NOS | 1/285 (0.4%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Anorexia | 2/285 (0.7%) | 2/409 (0.5%) | 5/420 (1.2%) | |||
| Blood bicarbonate decreased | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Dehydration | 5/285 (1.8%) | 3/409 (0.7%) | 7/420 (1.7%) | |||
| Hyperglycaemia NOS | 0/285 (0%) | 6/409 (1.5%) | 2/420 (0.5%) | |||
| Hyperkalaemia | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Hypoalbuminemia | 3/285 (1.1%) | 2/409 (0.5%) | 4/420 (1%) | |||
| Hypocalcemia | 2/285 (0.7%) | 0/409 (0%) | 0/420 (0%) | |||
| Hypoglycemia NOS | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Hypokalemia | 3/285 (1.1%) | 4/409 (1%) | 6/420 (1.4%) | |||
| Hypomagnesemia | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Hyponatremia | 5/285 (1.8%) | 6/409 (1.5%) | 1/420 (0.2%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Chest wall pain | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Muscle weakness NOS | 2/285 (0.7%) | 2/409 (0.5%) | 10/420 (2.4%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-upper | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Right-sided | 0/285 (0%) | 1/409 (0.2%) | 2/420 (0.5%) | |||
| Musculoskeletal/soft tissue - Other: | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Neck pain | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Pain in extremity | 1/285 (0.4%) | 2/409 (0.5%) | 3/420 (0.7%) | |||
| Nervous system disorders | ||||||
| Ataxia | 0/285 (0%) | 0/409 (0%) | 4/420 (1%) | |||
| CNS necrosis/cystic progression: | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Cerebral ischaemia | 3/285 (1.1%) | 3/409 (0.7%) | 4/420 (1%) | |||
| Cerebrospinal fluid leak | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Cognitive disorder | 0/285 (0%) | 1/409 (0.2%) | 5/420 (1.2%) | |||
| Convulsions NOS | 9/285 (3.2%) | 23/409 (5.6%) | 24/420 (5.7%) | |||
| Depressed level of consciousness | 2/285 (0.7%) | 2/409 (0.5%) | 3/420 (0.7%) | |||
| Diaphragmatic paralysis | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Dizziness | 2/285 (0.7%) | 5/409 (1.2%) | 3/420 (0.7%) | |||
| Dysgeusia | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Encephalopathy | 1/285 (0.4%) | 1/409 (0.2%) | 2/420 (0.5%) | |||
| Extrapyramidal disorder | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Headache | 6/285 (2.1%) | 9/409 (2.2%) | 7/420 (1.7%) | |||
| Hemorrhagic stroke | 4/285 (1.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Hydrocephalus acquired | 0/285 (0%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Hyperreflexia | 2/285 (0.7%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Memory impairment | 1/285 (0.4%) | 3/409 (0.7%) | 3/420 (0.7%) | |||
| Mental status changes | 1/285 (0.4%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Facial | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Neuralgia NOS | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Neurology - Other: | 4/285 (1.4%) | 3/409 (0.7%) | 4/420 (1%) | |||
| Neuropathy: cranial: CN VIII Hearing and balance | 1/285 (0.4%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Peripheral motor neuropathy | 1/285 (0.4%) | 8/409 (2%) | 7/420 (1.7%) | |||
| Peripheral sensory neuropathy | 1/285 (0.4%) | 1/409 (0.2%) | 2/420 (0.5%) | |||
| Speech disorder | 1/285 (0.4%) | 3/409 (0.7%) | 2/420 (0.5%) | |||
| Syncope | 1/285 (0.4%) | 1/409 (0.2%) | 2/420 (0.5%) | |||
| Syncope vasovagal | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Tremor | 0/285 (0%) | 1/409 (0.2%) | 1/420 (0.2%) | |||
| Psychiatric disorders | ||||||
| Agitation | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Anxiety | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Confusional state | 5/285 (1.8%) | 12/409 (2.9%) | 10/420 (2.4%) | |||
| Depression | 1/285 (0.4%) | 4/409 (1%) | 4/420 (1%) | |||
| Insomnia | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Libido decreased | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Personality change | 0/285 (0%) | 3/409 (0.7%) | 0/420 (0%) | |||
| Psychosis aggravated | 1/285 (0.4%) | 2/409 (0.5%) | 0/420 (0%) | |||
| Renal and urinary disorders | ||||||
| Cystitis NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Renal failure NOS | 2/285 (0.7%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Urinary incontinence | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Urinary retention | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Erectile dysfunction NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Scrotal pain | 1/285 (0.4%) | 0/409 (0%) | 0/420 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Aspiration | 0/285 (0%) | 2/409 (0.5%) | 1/420 (0.2%) | |||
| Cough | 0/285 (0%) | 0/409 (0%) | 3/420 (0.7%) | |||
| Dyspnoea | 7/285 (2.5%) | 5/409 (1.2%) | 7/420 (1.7%) | |||
| Hypoxia | 3/285 (1.1%) | 1/409 (0.2%) | 6/420 (1.4%) | |||
| Nasal cavity/paranasal sinus reactions: | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Pleural effusion | 3/285 (1.1%) | 0/409 (0%) | 0/420 (0%) | |||
| Pneumonitis NOS | 7/285 (2.5%) | 4/409 (1%) | 6/420 (1.4%) | |||
| Pulmonary/upper respiratory - Other: | 1/285 (0.4%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Respiratory tract hemorrhage NOS | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne NOS | 1/285 (0.4%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Dermatitis exfoliative NOS | 1/285 (0.4%) | 1/409 (0.2%) | 3/420 (0.7%) | |||
| Pain of skin | 0/285 (0%) | 0/409 (0%) | 1/420 (0.2%) | |||
| Petechiae | 0/285 (0%) | 1/409 (0.2%) | 0/420 (0%) | |||
| Vascular disorders | ||||||
| Hematoma | 0/285 (0%) | 0/409 (0%) | 2/420 (0.5%) | |||
| Hypotension NOS | 3/285 (1.1%) | 1/409 (0.2%) | 3/420 (0.7%) | |||
| Thrombosis | 15/285 (5.3%) | 15/409 (3.7%) | 19/420 (4.5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| No Adjuvant TMZ (Not Randomized) | Conventional Adjuvant TMZ | Dose-dense Adjuvant TMZ | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 216/285 (75.8%) | 376/409 (91.9%) | 392/420 (93.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Hemoglobin | 69/285 (24.2%) | 142/409 (34.7%) | 171/420 (40.7%) | |||
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 8/285 (2.8%) | 27/409 (6.6%) | 20/420 (4.8%) | |||
| Eye disorders | ||||||
| Ocular/visual - Other: | 16/285 (5.6%) | 37/409 (9%) | 27/420 (6.4%) | |||
| Vision blurred | 19/285 (6.7%) | 48/409 (11.7%) | 54/420 (12.9%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain NOS | 5/285 (1.8%) | 17/409 (4.2%) | 25/420 (6%) | |||
| Constipation | 58/285 (20.4%) | 135/409 (33%) | 129/420 (30.7%) | |||
| Diarrhoea NOS | 12/285 (4.2%) | 50/409 (12.2%) | 75/420 (17.9%) | |||
| Dry mouth | 7/285 (2.5%) | 22/409 (5.4%) | 26/420 (6.2%) | |||
| Dyspepsia | 11/285 (3.9%) | 30/409 (7.3%) | 32/420 (7.6%) | |||
| Nausea | 79/285 (27.7%) | 226/409 (55.3%) | 228/420 (54.3%) | |||
| Stomatitis | 9/285 (3.2%) | 20/409 (4.9%) | 24/420 (5.7%) | |||
| Vomiting NOS | 32/285 (11.2%) | 114/409 (27.9%) | 117/420 (27.9%) | |||
| General disorders | ||||||
| Edema: head and neck: | 7/285 (2.5%) | 15/409 (3.7%) | 27/420 (6.4%) | |||
| Edema: limb: | 18/285 (6.3%) | 49/409 (12%) | 54/420 (12.9%) | |||
| Fatigue | 134/285 (47%) | 292/409 (71.4%) | 320/420 (76.2%) | |||
| Pain - Other: | 3/285 (1.1%) | 29/409 (7.1%) | 23/420 (5.5%) | |||
| Pyrexia | 8/285 (2.8%) | 25/409 (6.1%) | 27/420 (6.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Dermatitis radiation NOS | 43/285 (15.1%) | 97/409 (23.7%) | 103/420 (24.5%) | |||
| Radiation recall syndrome | 10/285 (3.5%) | 20/409 (4.9%) | 26/420 (6.2%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 41/285 (14.4%) | 100/409 (24.4%) | 109/420 (26%) | |||
| Aspartate aminotransferase increased | 21/285 (7.4%) | 64/409 (15.6%) | 70/420 (16.7%) | |||
| Blood alkaline phosphatase increased | 17/285 (6%) | 46/409 (11.2%) | 49/420 (11.7%) | |||
| Blood creatinine increased | 7/285 (2.5%) | 25/409 (6.1%) | 32/420 (7.6%) | |||
| CD4 lymphocytes decreased | 0/285 (0%) | 13/409 (3.2%) | 32/420 (7.6%) | |||
| Leukopenia NOS | 44/285 (15.4%) | 152/409 (37.2%) | 190/420 (45.2%) | |||
| Lymphopenia | 49/285 (17.2%) | 170/409 (41.6%) | 179/420 (42.6%) | |||
| Metabolic/laboratory - Other: | 16/285 (5.6%) | 39/409 (9.5%) | 38/420 (9%) | |||
| Neutrophil count | 18/285 (6.3%) | 89/409 (21.8%) | 107/420 (25.5%) | |||
| Platelet count decreased | 53/285 (18.6%) | 161/409 (39.4%) | 163/420 (38.8%) | |||
| Weight decreased | 12/285 (4.2%) | 54/409 (13.2%) | 73/420 (17.4%) | |||
| Metabolism and nutrition disorders | ||||||
| Anorexia | 48/285 (16.8%) | 113/409 (27.6%) | 140/420 (33.3%) | |||
| Hyperglycaemia NOS | 50/285 (17.5%) | 116/409 (28.4%) | 130/420 (31%) | |||
| Hypernatremia | 4/285 (1.4%) | 21/409 (5.1%) | 20/420 (4.8%) | |||
| Hypoalbuminemia | 20/285 (7%) | 46/409 (11.2%) | 56/420 (13.3%) | |||
| Hypocalcemia | 20/285 (7%) | 39/409 (9.5%) | 45/420 (10.7%) | |||
| Hypoglycemia NOS | 4/285 (1.4%) | 21/409 (5.1%) | 22/420 (5.2%) | |||
| Hypokalemia | 18/285 (6.3%) | 46/409 (11.2%) | 51/420 (12.1%) | |||
| Hyponatremia | 22/285 (7.7%) | 48/409 (11.7%) | 60/420 (14.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4/285 (1.4%) | 27/409 (6.6%) | 32/420 (7.6%) | |||
| Back pain | 9/285 (3.2%) | 23/409 (5.6%) | 23/420 (5.5%) | |||
| Muscle weakness NOS | 19/285 (6.7%) | 41/409 (10%) | 49/420 (11.7%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower | 11/285 (3.9%) | 33/409 (8.1%) | 26/420 (6.2%) | |||
| Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided | 4/285 (1.4%) | 24/409 (5.9%) | 16/420 (3.8%) | |||
| Myalgia | 5/285 (1.8%) | 13/409 (3.2%) | 24/420 (5.7%) | |||
| Pain in extremity | 11/285 (3.9%) | 22/409 (5.4%) | 30/420 (7.1%) | |||
| Nervous system disorders | ||||||
| Ataxia | 23/285 (8.1%) | 56/409 (13.7%) | 54/420 (12.9%) | |||
| Cognitive disorder | 11/285 (3.9%) | 31/409 (7.6%) | 37/420 (8.8%) | |||
| Convulsions NOS | 34/285 (11.9%) | 80/409 (19.6%) | 87/420 (20.7%) | |||
| Depressed level of consciousness | 8/285 (2.8%) | 15/409 (3.7%) | 23/420 (5.5%) | |||
| Dizziness | 25/285 (8.8%) | 93/409 (22.7%) | 75/420 (17.9%) | |||
| Dysgeusia | 19/285 (6.7%) | 43/409 (10.5%) | 63/420 (15%) | |||
| Headache | 69/285 (24.2%) | 193/409 (47.2%) | 199/420 (47.4%) | |||
| Hyperreflexia | 9/285 (3.2%) | 24/409 (5.9%) | 23/420 (5.5%) | |||
| Memory impairment | 29/285 (10.2%) | 84/409 (20.5%) | 85/420 (20.2%) | |||
| Neurology - Other: | 7/285 (2.5%) | 34/409 (8.3%) | 34/420 (8.1%) | |||
| Peripheral motor neuropathy | 33/285 (11.6%) | 58/409 (14.2%) | 64/420 (15.2%) | |||
| Peripheral sensory neuropathy | 20/285 (7%) | 58/409 (14.2%) | 64/420 (15.2%) | |||
| Speech disorder | 34/285 (11.9%) | 65/409 (15.9%) | 64/420 (15.2%) | |||
| Tremor | 9/285 (3.2%) | 54/409 (13.2%) | 44/420 (10.5%) | |||
| Psychiatric disorders | ||||||
| Agitation | 3/285 (1.1%) | 27/409 (6.6%) | 17/420 (4%) | |||
| Anxiety | 15/285 (5.3%) | 50/409 (12.2%) | 41/420 (9.8%) | |||
| Confusional state | 32/285 (11.2%) | 57/409 (13.9%) | 59/420 (14%) | |||
| Depression | 19/285 (6.7%) | 55/409 (13.4%) | 62/420 (14.8%) | |||
| Insomnia | 39/285 (13.7%) | 85/409 (20.8%) | 77/420 (18.3%) | |||
| Renal and urinary disorders | ||||||
| Pollakiuria | 5/285 (1.8%) | 21/409 (5.1%) | 21/420 (5%) | |||
| Urinary incontinence | 8/285 (2.8%) | 14/409 (3.4%) | 22/420 (5.2%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 14/285 (4.9%) | 49/409 (12%) | 53/420 (12.6%) | |||
| Dyspnoea | 15/285 (5.3%) | 35/409 (8.6%) | 37/420 (8.8%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 86/285 (30.2%) | 173/409 (42.3%) | 191/420 (45.5%) | |||
| Dermatitis exfoliative NOS | 13/285 (4.6%) | 63/409 (15.4%) | 76/420 (18.1%) | |||
| Pruritus | 15/285 (5.3%) | 45/409 (11%) | 53/420 (12.6%) | |||
Limitations/Caveats
Only participants registered after 07-12-2007 were able to participate in the quality of life / patient reported outcome study components.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Wendy Seiferheld |
|---|---|
| Organization | Radiation Therapy Oncology Group (RTOG) |
| Phone | |
| wseiferheld@acr.org |
Responsible Party:
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00304031
Other Study ID Numbers:
- RTOG-0525
- CDR0000465183
- EORTC-26052
- EORTC-22053
- NCI-2009-00731
First Posted:
Mar 17, 2006
Last Update Posted:
Jun 9, 2020
Last Verified:
May 1, 2020