Back to resultsG-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
Primary Purpose
Lung Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Filgrastim
Pegfilgrastim
Etoposide
Cisplatin
radiation therapy
Sponsored by
About this trial
This is an interventional supportive care trial for Lung Cancer focused on measuring limited stage small cell lung cancer
Eligibility 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
Sites / Locations
- University of Florida Shands Cancer Center
- CCOP - Mount Sinai Medical Center
- Lucille P. Markey Cancer Center at University of Kentucky
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Northern Rockies Radiation Oncology Center
- Methodist Estabrook Cancer Center
- McDowell Cancer Center at Akron General Medical Center
- Summa Center for Cancer Care at Akron City Hospital
- Charles M. Barrett Cancer Center at University Hospital
- Cleveland Clinic Taussig Cancer Center
- Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
- Cancer Treatment Center
- McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
- Veterans Affairs Medical Center - Milwaukee
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combined Modality Therapy with Growth Factor Support
Arm Description
Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim.
Outcomes
Primary Outcome Measures
Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy
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
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
Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events
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
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
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
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.
Full Information
NCT ID
NCT00554463
First Posted
November 6, 2007
Last Updated
May 16, 2019
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), Cancer and Leukemia Group B
1. Study Identification
Unique Protocol Identification Number
NCT00554463
Brief Title
G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
Official Title
A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 3, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), Cancer and Leukemia Group B
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
limited stage small cell lung cancer
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combined Modality Therapy with Growth Factor Support
Arm Type
Experimental
Arm Description
Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim.
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Intervention Description
5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Intervention Description
6 mg via subcutaneous injection days 46 and 67
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Concurrent: 60 mg/m^2, IV on days 1 and 22. Adjuvant: 60 mg/m^2, IV on days 43 and 64.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
Title
Number of Patients With Dose Modifications or Treatment Delays
Time Frame
From start of treatment to end of treatment, for a maximum of 66 days
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rogerio C. Lilenbaum, MD
Organizational Affiliation
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ritsuko U. Komaki, MD, FACR
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Michael A. Samuels, MD
Organizational Affiliation
CCOP - Mount Sinai Medical Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jeffrey Crawford, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
University of Florida Shands Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0232
Country
United States
Facility Name
CCOP - Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Lucille P. Markey Cancer Center at University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0093
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
Facility Name
Northern Rockies Radiation Oncology Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Methodist Estabrook Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
McDowell Cancer Center at Akron General Medical Center
City
Akron
State/Province
Ohio
ZIP/Postal Code
44307
Country
United States
Facility Name
Summa Center for Cancer Care at Akron City Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44309-2090
Country
United States
Facility Name
Charles M. Barrett Cancer Center at University Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
City
Salem
State/Province
Ohio
ZIP/Postal Code
44460
Country
United States
Facility Name
Cancer Treatment Center
City
Wooster
State/Province
Ohio
ZIP/Postal Code
44691
Country
United States
Facility Name
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
City
Reading
State/Province
Pennsylvania
ZIP/Postal Code
19612-6052
Country
United States
Facility Name
Veterans Affairs Medical Center - Milwaukee
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20421820
Citation
Lilenbaum R, Samuels M, Taffaro-Neskey M, Cusnir M, Pizzolato J, Blaustein A. Phase II trial of combined modality therapy with myeloid growth factor support in patients with locally advanced non-small cell lung cancer. J Thorac Oncol. 2010 Jun;5(6):837-40. doi: 10.1097/JTO.0b013e3181d6e141.
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G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
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