G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer

Study Overview
=================
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.

Official Title
-----------------
A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: Filgrastim
* Drug: Pegfilgrastim
* Drug: Etoposide
* Drug: Cisplatin
* Radiation: radiation therapy


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Modality Therapy with Growth Factor Support<br>Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim. | Drug: Filgrastim<br>* 5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.<br>Drug: Pegfilgrastim<br>* 6 mg via subcutaneous injection days 46 and 67<br>Drug: Etoposide<br>* 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.<br>Drug: Cisplatin<br>* Concurrent: 60 mg/m^2, IV on days 1 and 22. Adjuvant: 60 mg/m^2, IV on days 43 and 64.<br>Radiation: radiation therapy<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From the start to the end of adjuvant chemotherapy, a maximum of 24 days | 
| 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 | 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. | From registration to last follow-up, a maximum of 32.9 months | 
| 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. | From registration to last follow-up, a maximum of 32.9 months | 
| 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. | From registration to last follow-up, a maximum of 32.9 months | 
| 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. | From registration to last follow-up, a maximum of 32.9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
limited stage small cell lung cancer