Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without filgrastim in treating patients who have extensive-stage small cell lung cancer that has not been previously treated.

Detailed Description
-----------------
OBJECTIVES: Determine the tolerability of topotecan and carboplatin with or without filgrastim (G-CSF) in patients with extensive stage small cell lung cancer. Determine response and survival rates in patients treated with these regimens. OUTLINE: This is a multicenter study. The first 12 patients are assigned to 1 of 2 treatment regimens (6 per regimen). The next 33 patients receive treatment based on the toxicity experienced by the first 12. Regimen A: Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover. Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, or no more than 1 patient experiences an absolute neutrophil count of less than 500/mm3 for more than 5 days, the next 6 patients begin treatment on regimen B. Otherwise, all patients receive treatment as in regimen A. Regimen B: Patients receive topotecan and carboplatin as in regimen A. Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A. Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes. Quality of life is assessed at baseline and at the beginning of each course of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study within 13.5 months.

Official Title
-----------------
Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF (Filgrastim) Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer

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

Intervention / Treatment
-----------------
* Biological: filgrastim
* Drug: carboplatin
* Drug: topotecan hydrochloride
* Radiation: WBRT


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed extensive stage small cell lung cancer Previously untreated with chemotherapy No mixed histology Metastatic disease outside the chest Contralateral supraclavicular or hilar nodes that cannot be included in a single radiation port OR Cytologically proven malignant pleural effusion Measurable disease No untreated CNS metastases CNS metastases treated with whole-brain radiotherapy (WBRT) allowed after completion of WBRT PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: AST no greater than 5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 5 times ULN Bilirubin no greater than 1.5 times ULN OR Direct bilirubin no greater than ULN Renal: Creatinine no greater than 1.5 times ULN OR Creatinine clearance at least 50 mL/min Cardiovascular: No uncontrolled angina pectoris No congestive heart failure within the past 3 months unless ejection fraction is greater than 40% No uncontrolled cardiac arrhythmias No myocardial infarction within the past 3 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No clinically significant infection No hypersensitivity to E. coli-derived proteins No other malignancy within the past 3 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 5 years since prior chemotherapy for another malignancy No prior nitrosoureas Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior thoracic radiotherapy At least 1 day since prior palliative radiotherapy (except to chest) No more than 3 fractions to chest for superior vena cava syndrome allowed No concurrent radiotherapy (including thoracic radiotherapy) Surgery: More than 3 weeks since prior major surgery

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: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover. Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes. Quality of life is assessed at baseline and at the beginning of each course of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. | Biological: filgrastim<br> <br> Drug: carboplatin<br> <br> Drug: topotecan hydrochloride<br> <br> Radiation: WBRT<br> <br> |
| Experimental: Regimen B<br>Patients receive topotecan and carboplatin as in regimen A. Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A. Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes. Quality of life is assessed at baseline and at the beginning of each course of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. | Biological: filgrastim<br> <br> Drug: carboplatin<br> <br> Drug: topotecan hydrochloride<br> <br> Radiation: WBRT<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | Up to 5 years | 

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