Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Study Details
Study Description
Brief Summary
This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.
-
Determine the safety and toxicity of this drug in these patients.
SECONDARY OBJECTIVES:
-
Determine the pharmacokinetics of this drug in these patients. II. Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.
-
Correlate genetic alteration of tumors with response in patients treated with this drug.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to planned surgery (yes [stratum 1] vs no [stratum 2]) and number of prior chemotherapy regimens for progressive/recurrent disease (≤ 1 [stratum 1A] vs ≥ 2 [stratum 1B]).
STRATUM 1: Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. (not undergoing surgery)
STRATUM 2: Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. (undergoing surgery)
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Stratum 1 (not undergoing surgery) Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Drug: vorinostat
Given orally
Other Names:
Procedure: conventional surgery
Patients undergo surgery to remove tumor
Other Names:
|
| Experimental: Stratum 2 (undergoing surgery) Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Drug: vorinostat
Given orally
Other Names:
Procedure: conventional surgery
Patients undergo surgery to remove tumor
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Successes (Patients Alive and Progression-free) [At 6 months]
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Secondary Outcome Measures
- Survival [From study registration to date of death due to any cause or last follow-up (up to 5 years)]
Estimated using Kaplan-Meier survival curve.
- Confirmed Tumor Response [Assessed up to 5 years]
A confirmed tumor response will be defined as an objective status of complete response (CR), partial response (PR), or regression (REGR) on two consecutive evaluations, which include neuroimaging, lasting during a period of at least 6 weeks. Confidence intervals for the true proportion will be calculated using the exact binomial method. Bidimensionally measurable disease:≥50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. Patient should be on stable or decreased steroid dose.
- Time to Progression [From registration to disease progression (up to 5 years)]
Estimated using Kaplan-Meier survival curve. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence
-
Progressive or recurrent disease
-
Measurable or evaluable disease by MRI or CT scan
-
Performance status - ECOG 0-2
-
WBC ≥ 3,000/mm^3
-
Absolute neutrophil count ≥ 1,500/mm^3
-
Platelet count ≥ 100,000/mm^3
-
Hemoglobin ≥ 8 g/dL
-
AST ≤ 3 times upper limit of normal (ULN)
-
Bilirubin normal
-
Creatinine ≤ 1.5 times ULN
-
No myocardial infarction within the past 6 months
-
No congestive heart failure
-
No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy
-
No known HIV positivity
-
Not immunocompromised except if related to the use of corticosteroids
-
No known hypersensitivity to any of the components of the study drug
-
No uncontrolled infection
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
-
No other malignancy
-
No other severe disease that would preclude study participation
-
Prior adjuvant chemotherapy allowed
-
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
-
More than 2 weeks since prior small molecule cell cycle inhibitor
-
Concurrent corticosteroids allowed as long as dose has been stable for ≥ 1 week
-
At least 8 weeks since prior radiotherapy
-
Must have evidence of tumor progression by MRI or CT scan after radiotherapy
-
More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless 1 of the following criteria is met:
-
There is a separate lesion by MRI outside of the prior treatment field
-
There is evidence of recurrent disease by biopsy, MRI spectroscopy, or positron-emission tomography scan
-
More than 2 weeks since prior valproic acid
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | North Central Cancer Treatment Group | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Evanthia Galanis, North Central Cancer Treatment Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00646
- NCI-2009-00646
- CDR0000445405
- NCCTG-N047B
- N047B
- N047B
- U10CA025224
- NCT01647100
Study Results
Participant Flow
| Recruitment Details | Participants were recruited from 24 medical clinics in the United States between September 2005 to May 2008. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) |
|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. |
| Period Title: Overall Study | |||
| STARTED | 68 | 15 | 20 |
| COMPLETED | 53 | 13 | 11 |
| NOT COMPLETED | 15 | 2 | 9 |
Baseline Characteristics
| Arm/Group Title | Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) | Total |
|---|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Total of all reporting groups |
| Overall Participants | 68 | 15 | 20 | 103 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
58
|
49
|
55.5
|
56
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
30
44.1%
|
4
26.7%
|
10
50%
|
44
42.7%
|
| Male |
38
55.9%
|
11
73.3%
|
10
50%
|
59
57.3%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
68
100%
|
15
100%
|
20
100%
|
103
100%
|
Outcome Measures
| Title | Proportion of Successes (Patients Alive and Progression-free) |
|---|---|
| Description | Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. |
| Time Frame | At 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 68 Stratum 1 patients were enrolled. 2 stratum 1 patients did not receive treatment. Therefore, the remaining 66 patients were analyzed. |
| Arm/Group Title | Stratum 1 Patients That Started Treatment | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) |
|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. |
| Measure Participants | 66 | 15 | 20 |
| Number (95% Confidence Interval) [percentage of participants] |
15.2
22.4%
|
26.7
178%
|
10
50%
|
| Title | Survival |
|---|---|
| Description | Estimated using Kaplan-Meier survival curve. |
| Time Frame | From study registration to date of death due to any cause or last follow-up (up to 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Stratum 1: 68 patients were enrolled. 2 patients did not receive treatment. Therefore, the remaining 66 patients were analyzed. The patient that survived 28 months was alive at last follow-up. |
| Arm/Group Title | Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) |
|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. |
| Measure Participants | 66 | 15 | 20 |
| Median (Full Range) [months] |
5.7
|
10.2
|
2.2
|
| Title | Confirmed Tumor Response |
|---|---|
| Description | A confirmed tumor response will be defined as an objective status of complete response (CR), partial response (PR), or regression (REGR) on two consecutive evaluations, which include neuroimaging, lasting during a period of at least 6 weeks. Confidence intervals for the true proportion will be calculated using the exact binomial method. Bidimensionally measurable disease:≥50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. Patient should be on stable or decreased steroid dose. |
| Time Frame | Assessed up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Stratum 1: 68 patients were enrolled. 2 patients did not receive treatment. Therefore, the remaining 66 patients were analyzed. Stratum 2: Since the patients underwent surgery, response is not applicable and hence 0 patients analyzed. |
| Arm/Group Title | Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) |
|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. |
| Measure Participants | 66 | 0 | 20 |
| Number (95% Confidence Interval) [percentage of participants] |
3.0
4.4%
|
0
0%
|
| Title | Time to Progression |
|---|---|
| Description | Estimated using Kaplan-Meier survival curve. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. |
| Time Frame | From registration to disease progression (up to 5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Stratum 1: 68 patients were enrolled. 2 stratum 1 patients did not receive treatment. Therefore, the remaining 66 patients were analyzed. The patient that survived 28 months was progression-free at last follow-up. |
| Arm/Group Title | Stratum 1 Patients That Started Treatment | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) |
|---|---|---|---|
| Arm/Group Description | Patients not receiving pre-surgery SAHA with ≤1 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | Beginning 3 days prior to surgery, patients receive oral vorinostat (SAHA) once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. surgery : Patients undergo surgery to remove tumor | Patients not receiving pre-surgery SAHA with ≥2 prior chemotherapy regimens for progressive/recurrent disease. Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. |
| Measure Participants | 66 | 15 | 20 |
| Median (Full Range) [months] |
1.9
|
3.7
|
1.4
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) | |||
| Arm/Group Description | vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | surgery : Patients undergo surgery to remove tumor | vorinostat : Given orally, 200 milligrams two times a day for 14 days followed by 7 days rest. | |||
All Cause Mortality |
||||||
| Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/66 (19.7%) | 3/15 (20%) | 4/20 (20%) | |||
| Cardiac disorders | ||||||
| Arrhythmia supraventricular | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Diarrhea | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Dysphagia | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Nausea | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vomiting | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| General disorders | ||||||
| Disease progression | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Fatigue | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Infections and infestations | ||||||
| Bladder infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Bronchitis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Mucosal infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pneumonia | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Amylase increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Leukocyte count decreased | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Lipase increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Neutrophil count decreased | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Platelet count decreased | 7/66 (10.6%) | 7 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Blood glucose increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Dehydration | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum phosphate decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum potassium decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum sodium decreased | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum sodium increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Muscle weakness left-sided | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Muscle weakness lower limb | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||||
| Central nervous system necrosis | 0/66 (0%) | 0 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Cognitive disturbance | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Depressed level of consciousness | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Dizziness | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Headache | 0/66 (0%) | 0 | 2/15 (13.3%) | 2 | 0/20 (0%) | 0 |
| Hydrocephalus | 1/66 (1.5%) | 1 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Intracranial hemorrhage | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Peripheral motor neuropathy | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Seizure | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Speech disorder | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Syncope | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Confusion | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Renal failure | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Hypotension | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Thrombosis | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Stratum 1 (Not Undergoing Surgery) | Stratum 2 (Undergoing Surgery) | Stratum 3 (Not Undergoing Surgery) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 65/66 (98.5%) | 14/15 (93.3%) | 19/20 (95%) | |||
| Blood and lymphatic system disorders | ||||||
| Hemoglobin decreased | 34/66 (51.5%) | 156 | 10/15 (66.7%) | 47 | 9/20 (45%) | 57 |
| Eye disorders | ||||||
| Diplopia | 0/66 (0%) | 0 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Vision blurred | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vitreous hemorrhage | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 12/66 (18.2%) | 41 | 3/15 (20%) | 4 | 1/20 (5%) | 1 |
| Constipation | 4/66 (6.1%) | 10 | 1/15 (6.7%) | 11 | 2/20 (10%) | 5 |
| Diarrhea | 21/66 (31.8%) | 63 | 7/15 (46.7%) | 27 | 8/20 (40%) | 12 |
| Dry mouth | 2/66 (3%) | 6 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Dyspepsia | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Dysphagia | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Esophageal mucositis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Esophagitis | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Flatulence | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Hemorrhoids | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Mucositis oral | 3/66 (4.5%) | 4 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Nausea | 17/66 (25.8%) | 52 | 8/15 (53.3%) | 13 | 7/20 (35%) | 15 |
| Oral hemorrhage | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Vomiting | 8/66 (12.1%) | 14 | 4/15 (26.7%) | 5 | 3/20 (15%) | 4 |
| General disorders | ||||||
| Chills | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Edema limbs | 3/66 (4.5%) | 4 | 1/15 (6.7%) | 2 | 0/20 (0%) | 0 |
| Fatigue | 57/66 (86.4%) | 192 | 11/15 (73.3%) | 72 | 16/20 (80%) | 46 |
| Fever | 2/66 (3%) | 3 | 1/15 (6.7%) | 3 | 0/20 (0%) | 0 |
| Gait abnormal | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Localized edema | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Infections and infestations | ||||||
| Abdominal infection | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Bladder infection | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Gingival infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Penile infection | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Pneumonia | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Sepsis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Sinusitis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Upper respiratory infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vaginal infection | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arterial injury - Extremity-lower | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vascular access complication | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 4/66 (6.1%) | 11 | 2/15 (13.3%) | 3 | 3/20 (15%) | 8 |
| Alkaline phosphatase increased | 7/66 (10.6%) | 42 | 1/15 (6.7%) | 1 | 2/20 (10%) | 6 |
| Aspartate aminotransferase increased | 11/66 (16.7%) | 19 | 2/15 (13.3%) | 2 | 3/20 (15%) | 8 |
| Blood bilirubin increased | 1/66 (1.5%) | 1 | 3/15 (20%) | 3 | 1/20 (5%) | 1 |
| CD4 lymphocytes decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Creatine phosphokinase increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Creatinine increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 8 |
| Laboratory test abnormal | 1/66 (1.5%) | 4 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Leukocyte count decreased | 26/66 (39.4%) | 109 | 9/15 (60%) | 32 | 5/20 (25%) | 31 |
| Lymphocyte count decreased | 5/66 (7.6%) | 21 | 0/15 (0%) | 0 | 2/20 (10%) | 2 |
| Neutrophil count decreased | 20/66 (30.3%) | 87 | 6/15 (40%) | 19 | 5/20 (25%) | 16 |
| Platelet count decreased | 45/66 (68.2%) | 198 | 12/15 (80%) | 33 | 17/20 (85%) | 55 |
| Serum cholesterol increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Weight gain | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Weight loss | 2/66 (3%) | 2 | 1/15 (6.7%) | 1 | 3/20 (15%) | 9 |
| Metabolism and nutrition disorders | ||||||
| Acidosis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Alkalosis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Anorexia | 18/66 (27.3%) | 43 | 5/15 (33.3%) | 22 | 10/20 (50%) | 18 |
| Blood bicarbonate decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Blood glucose increased | 22/66 (33.3%) | 37 | 1/15 (6.7%) | 1 | 3/20 (15%) | 37 |
| Dehydration | 6/66 (9.1%) | 10 | 2/15 (13.3%) | 2 | 1/20 (5%) | 1 |
| Serum albumin decreased | 4/66 (6.1%) | 6 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Serum calcium decreased | 4/66 (6.1%) | 7 | 1/15 (6.7%) | 1 | 1/20 (5%) | 2 |
| Serum calcium increased | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Serum glucose decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum magnesium increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum phosphate decreased | 1/66 (1.5%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum potassium decreased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Serum potassium increased | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 2 |
| Serum sodium decreased | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 2/20 (10%) | 7 |
| Serum sodium increased | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Back pain | 1/66 (1.5%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Muscle weakness | 7/66 (10.6%) | 7 | 0/15 (0%) | 0 | 3/20 (15%) | 4 |
| Muscle weakness left-sided | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Muscle weakness lower limb | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 1/20 (5%) | 2 |
| Muscle weakness right-sided | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Myalgia | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pain in extremity | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Treatment related secondary malignancy | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||||
| Accessory nerve disorder | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Ataxia | 7/66 (10.6%) | 9 | 0/15 (0%) | 0 | 1/20 (5%) | 2 |
| Cognitive disturbance | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 4 |
| Depressed level of consciousness | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 2/20 (10%) | 2 |
| Dizziness | 5/66 (7.6%) | 5 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Dysgeusia | 15/66 (22.7%) | 51 | 3/15 (20%) | 14 | 4/20 (20%) | 6 |
| Extrapyramidal disorder | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Headache | 12/66 (18.2%) | 21 | 3/15 (20%) | 3 | 2/20 (10%) | 3 |
| Ischemia cerebrovascular | 0/66 (0%) | 0 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Memory impairment | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 4 |
| Neurological disorder NOS | 1/66 (1.5%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Peripheral motor neuropathy | 1/66 (1.5%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 34 |
| Peripheral sensory neuropathy | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 1/20 (5%) | 11 |
| Seizure | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 2/20 (10%) | 2 |
| Sinus pain | 0/66 (0%) | 0 | 1/15 (6.7%) | 6 | 0/20 (0%) | 0 |
| Speech disorder | 7/66 (10.6%) | 7 | 0/15 (0%) | 0 | 1/20 (5%) | 19 |
| Syncope | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Confusion | 3/66 (4.5%) | 4 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Depression | 2/66 (3%) | 4 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Insomnia | 1/66 (1.5%) | 4 | 1/15 (6.7%) | 9 | 1/20 (5%) | 1 |
| Libido decreased | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Renal and urinary disorders | ||||||
| Hemorrhage urinary tract | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Urinary frequency | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Urogenital disorder | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 1/20 (5%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Aspiration | 0/66 (0%) | 0 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Cough | 1/66 (1.5%) | 1 | 1/15 (6.7%) | 2 | 2/20 (10%) | 4 |
| Dyspnea | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Hiccups | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Hypoxia | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Laryngeal mucositis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pharyngolaryngeal pain | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pneumonitis | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pulmonary hypertension | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 2/66 (3%) | 7 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Dry skin | 2/66 (3%) | 21 | 1/15 (6.7%) | 7 | 0/20 (0%) | 0 |
| Erythema multiforme | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Petechiae | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Pruritus | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Rash desquamating | 2/66 (3%) | 3 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Vascular disorders | ||||||
| Hemorrhage | 0/66 (0%) | 0 | 1/15 (6.7%) | 1 | 0/20 (0%) | 0 |
| Hypertension | 1/66 (1.5%) | 1 | 0/15 (0%) | 0 | 0/20 (0%) | 0 |
| Hypotension | 2/66 (3%) | 2 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
| Thrombosis | 3/66 (4.5%) | 3 | 0/15 (0%) | 0 | 1/20 (5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Evanthia Galanis, M.D. |
|---|---|
| Organization | Mayo Clinic |
| Phone | (507) 284-3902 |
| galanis.evanthia@mayo.edu |
- NCI-2009-00646
- NCI-2009-00646
- CDR0000445405
- NCCTG-N047B
- N047B
- N047B
- U10CA025224
- NCT01647100