G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Colony-stimulating factors, such as G-CSF or pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy and radiation therapy.
PURPOSE: This phase II trial is studying G-CSF and pegfilgrastim to see how well they work in treating neutropenia in patients undergoing combination chemotherapy and radiation therapy for limited stage small cell lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
- To evaluate the safety and efficacy of filgrastim (G-CSF) in reducing grade 4 neutropenia or grades 3-4 febrile neutropenia in patients with limited stage small cell lung cancer treated with radiotherapy and concurrent chemotherapy comprising cisplatin and etoposide.
Secondary
-
To evaluate the safety and efficacy of pegfilgrastim in reducing grade 4 neutropenia or grades 3-4 febrile neutropenia in patients treated with adjuvant chemotherapy comprising cisplatin and etoposide.
-
To estimate the incidence of dose modifications or treatment delays in patients treated with this regimen.
-
To estimate the incidence of esophagitis, pneumonitis, and other non-hematological adverse events in patients treated with this regimen.
-
To estimate the incidence of grade 4 thrombocytopenia in patients treated with this regimen.
-
To estimate the median and two-year rate of progression-free and overall survival of patients treated with this regimen.
After completion of study therapy, patients are followed every 3 months for one year, every 6 months for 2-3 years, and then annually for up to 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Combined Modality Therapy with Growth Factor Support Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
Drug: Filgrastim
5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.
Drug: Pegfilgrastim
6 mg via subcutaneous injection days 46 and 67
Drug: Etoposide
Concurrent: 120 mg/m^2, IV on days 1-3 and days 22-24. Adjuvant: 120 mg/m^2, IV on days 43-45 and days 65-66.
Drug: Cisplatin
Concurrent: 60 mg/m^2, IV on days 1 and 22. Adjuvant: 60 mg/m^2, IV on days 43 and 64.
Radiation: radiation therapy
A total of 61.2 Gy in 5 weeks: Once-daily 1.8 Gy fractions for 15 fractions over 3 weeks beginning on day 1 of chemotherapy, then twice-daily 1.8 Gy fractions for 10 fractions over 2 weeks.
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy [From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days]
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. No testing was done due to early study termination.
Secondary Outcome Measures
- Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy [From the start to the end of adjuvant chemotherapy, a maximum of 24 days]
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.
- Number of Patients With Dose Modifications or Treatment Delays [From start of treatment to end of treatment, for a maximum of 66 days]
- Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events [From registration to last follow-up, a maximum of 32.9 months]
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. No testing was done due to early study termination.
- Number of Patients With Grade 4 Thrombocytopenia [From registration to last follow-up, a maximum of 32.9 months]
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.
- Overall Survival [From registration to last follow-up, a maximum of 32.9 months]
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. Due to early termination with few patients, only counts of events have been calculated.
- Progression-free Survival [From registration to last follow-up, a maximum of 32.9 months]
Progression is defined as any failure per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. 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. Due to early termination with few patients, only counts of events have been calculated.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically or cytologically confirmed small cell carcinoma of the lung
-
Limited stage disease, defined as any of the following:
-
Tumor confined to one hemithorax
-
T4 tumor not based on malignant pleural effusion
-
N3 disease not based on contralateral supraclavicular involvement
-
No complete tumor resection
-
Measurable or evaluable disease
-
Pleural effusion allowed provided the following conditions are present:
-
Effusion is too small to tap under CT guidance and is not evident on chest x-ray
-
Effusion appears only after a thoracotomy or other invasive procedure
-
Must have certification by a Radiation Oncologist that the tumor can be encompassed by limited radiotherapy fields without significantly compromising pulmonary function
-
No distant metastases
PATIENT CHARACTERISTICS:
-
Zubrod performance status 0-1
-
ANC (absolute neutrophil count) ≥ 1,800 cells/mm³
-
Platelet count ≥ 100,000 cells/mm³
-
Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL allowed)
-
Total bilirubin ≤ 1.5 mg/dL
-
AST (aspartate aminotransferase) or ALT (alanine amino transferase ) ≤ 2 times the upper limit of normal (ULN)
-
Alkaline phosphatase < 2.5 times ULN (< 5 times ULN if judged by the investigator to be related to liver metastases)
-
Serum creatinine ≤ 1.5 mg/dL
-
Creatinine clearance ≥ 50 mL/min
-
FEV1 (Forced Expiratory Volume) obtained pre- or post-bronchodilator must be ≥ 1.5 liters/second
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for ≥ 60 days after the last study treatment
-
No prior invasive malignancy, except non-melanomatous skin cancer or other micro-invasive malignancy, or carcinoma in situ of the breast, oral cavity, or cervix, unless the patient has been disease-free for a minimum of 3 years
-
No weight loss > 5% for any reason within the past 3 months
-
No severe, active comorbidity, defined as follows:
-
Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
-
Transmural myocardial infarction within the past 6 months
-
Acute bacterial or fungal infection requiring intravenous antibiotics
-
Chronic Obstructive Pulmonary Disease exacerbation with FEV1 (forced expiratory volume) < 1.5 liters/second or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
-
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
-
AIDS (HIV testing not required for entry into this protocol)
-
No prior allergic reaction to the study drugs
PRIOR CONCURRENT THERAPY:
-
No prior systemic chemotherapy for lung cancer
-
Prior chemotherapy for a different cancer is allowed, provided it was completed ≥ 5 years prior to registration
-
No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
-
No concurrent intensity-modulated radiotherapy
-
No concurrent amifostine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Florida Shands Cancer Center | Gainesville | Florida | United States | 32610-0232 |
| 2 | CCOP - Mount Sinai Medical Center | Miami Beach | Florida | United States | 33140 |
| 3 | Lucille P. Markey Cancer Center at University of Kentucky | Lexington | Kentucky | United States | 40536-0093 |
| 4 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | United States | 21231-2410 |
| 5 | Northern Rockies Radiation Oncology Center | Billings | Montana | United States | 59101 |
| 6 | Methodist Estabrook Cancer Center | Omaha | Nebraska | United States | 68114 |
| 7 | McDowell Cancer Center at Akron General Medical Center | Akron | Ohio | United States | 44307 |
| 8 | Summa Center for Cancer Care at Akron City Hospital | Akron | Ohio | United States | 44309-2090 |
| 9 | Charles M. Barrett Cancer Center at University Hospital | Cincinnati | Ohio | United States | 45267 |
| 10 | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | United States | 44195 |
| 11 | Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford | Salem | Ohio | United States | 44460 |
| 12 | Cancer Treatment Center | Wooster | Ohio | United States | 44691 |
| 13 | McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center | Reading | Pennsylvania | United States | 19612-6052 |
| 14 | Veterans Affairs Medical Center - Milwaukee | Milwaukee | Wisconsin | United States | 53295 |
Sponsors and Collaborators
- Radiation Therapy Oncology Group
- National Cancer Institute (NCI)
- Cancer and Leukemia Group B
Investigators
- Principal Investigator: Rogerio C. Lilenbaum, MD, Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
- Study Chair: Ritsuko U. Komaki, MD, FACR, M.D. Anderson Cancer Center
- Study Chair: Michael A. Samuels, MD, CCOP - Mount Sinai Medical Center
- Study Chair: Jeffrey Crawford, MD, Duke Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
- RTOG 0623
- CDR0000574000
- NCI-2009-00742
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Overall Participants | 5 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
67
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
80%
|
| Male |
1
20%
|
Outcome Measures
| Title | Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy |
|---|---|
| Description | 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. No testing was done due to early study termination. |
| Time Frame | From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy |
|---|---|
| Description | 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. |
| Time Frame | From the start to the end of adjuvant chemotherapy, a maximum of 24 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
1
20%
|
| Title | Number of Patients With Dose Modifications or Treatment Delays |
|---|---|
| Description | |
| Time Frame | From start of treatment to end of treatment, for a maximum of 66 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
2
40%
|
| Title | Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events |
|---|---|
| Description | 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. No testing was done due to early study termination. |
| Time Frame | From registration to last follow-up, a maximum of 32.9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Grade 3+ Esophagitis |
0
0%
|
| Grade 3+ Pneumonitis |
1
20%
|
| Grade 3+ Other non-hematologic |
1
20%
|
| Title | Number of Patients With Grade 4 Thrombocytopenia |
|---|---|
| Description | 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. |
| Time Frame | From registration to last follow-up, a maximum of 32.9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
0
0%
|
| Title | Overall Survival |
|---|---|
| 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. Due to early termination with few patients, only counts of events have been calculated. |
| Time Frame | From registration to last follow-up, a maximum of 32.9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
3
60%
|
| Title | Progression-free Survival |
|---|---|
| Description | Progression is defined as any failure per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. 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. Due to early termination with few patients, only counts of events have been calculated. |
| Time Frame | From registration to last follow-up, a maximum of 32.9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All registered patients |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support |
|---|---|
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. |
| Measure Participants | 5 |
| Count of Participants [Participants] |
3
60%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | Patients experiencing more than one of a given adverse event are counted only once for that adverse event. | |
| Arm/Group Title | Combined Modality Therapy With Growth Factor Support | |
| Arm/Group Description | Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. | |
All Cause Mortality |
||
| Combined Modality Therapy With Growth Factor Support | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Combined Modality Therapy With Growth Factor Support | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/5 (40%) | |
| Blood and lymphatic system disorders | ||
| Blood disorder | 1/5 (20%) | |
| Febrile neutropenia | 1/5 (20%) | |
| Hemoglobin decreased | 1/5 (20%) | |
| General disorders | ||
| Fatigue | 1/5 (20%) | |
| Infections and infestations | ||
| Sepsis [with Grade 3-4 ANC] | 1/5 (20%) | |
| Investigations | ||
| Neutrophil count decreased | 1/5 (20%) | |
| Nervous system disorders | ||
| Neurological disorder NOS | 1/5 (20%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Atelectasis | 1/5 (20%) | |
| Pneumonitis | 2/5 (40%) | |
Other (Not Including Serious) Adverse Events |
||
| Combined Modality Therapy With Growth Factor Support | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | |
| Cardiac disorders | ||
| Atrial flutter | 1/5 (20%) | |
| Pericardial effusion | 1/5 (20%) | |
| Sinus tachycardia | 1/5 (20%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/5 (20%) | |
| Constipation | 1/5 (20%) | |
| Dysphagia | 2/5 (40%) | |
| Esophagitis | 3/5 (60%) | |
| Gastrointestinal disorder | 1/5 (20%) | |
| Nausea | 3/5 (60%) | |
| Salivary gland disorder | 1/5 (20%) | |
| General disorders | ||
| Fatigue | 3/5 (60%) | |
| Infections and infestations | ||
| Bronchitis [with Grade 3-4 ANC] | 1/5 (20%) | |
| Sepsis [with unknown ANC] | 1/5 (20%) | |
| Investigations | ||
| Neutrophil count decreased | 2/5 (40%) | |
| Platelet count decreased | 2/5 (40%) | |
| Musculoskeletal and connective tissue disorders | ||
| Bone pain | 1/5 (20%) | |
| Muscle weakness | 1/5 (20%) | |
| Pain in extremity | 1/5 (20%) | |
| Nervous system disorders | ||
| Dizziness | 1/5 (20%) | |
| Headache | 1/5 (20%) | |
| Psychiatric disorders | ||
| Insomnia | 1/5 (20%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/5 (20%) | |
| Dyspnea | 1/5 (20%) | |
| Pneumonitis | 2/5 (40%) | |
| Respiratory disorder | 1/5 (20%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/5 (20%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Results Point of Contact
| Name/Title | Wendy Seiferheld |
|---|---|
| Organization | NRG Onocology |
| Phone | |
| wseiferheld@nrgonology.org |
- RTOG 0623
- CDR0000574000
- NCI-2009-00742