Carboplatin and Etoposide With or Without Thalidomide in Treating Patients With Limited-Stage or Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as carboplatin and etoposide use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy is more effective with or without thalidomide in treating small cell lung cancer. PURPOSE: This randomized phase III trial is studying carboplatin, etoposide, and thalidomide to see how well they work compared to carboplatin and etoposide in treating patients with limited- or extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the survival of patients with limited or extensive stage small cell lung cancer treated with carboplatin and etoposide with vs without thalidomide. Compare the time to disease progression in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the response rates of patients treated with these regimens. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (limited vs extensive), ECOG performance status (0 and 1 vs 2), and alkaline phosphatase (no greater than 1.5 times upper limit of normal [ULN] vs greater than 1.5 times ULN). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive carboplatin IV over 30 minutes on day 1 and etoposide* IV over 1-2 hours on days 1 and 2 and orally on day 3. Patients also receive oral thalidomide daily beginning on day 1. Arm II: Patients receive carboplatin and etoposide as in arm I and oral placebo daily beginning on day 1. NOTE: *Patients who are unable to receive etoposide IV on day 2 may receive oral etoposide on days 2 and 3. In both arms, chemotherapy (carboplatin and etoposide) repeats every 3 weeks for up to 6 courses. Patients receive thalidomide or placebo continuously for up to 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may continue to receive thalidomide or placebo provided the patient is clinically and symptomatically stable. Quality of life is assessed at baseline, during each course of chemotherapy, at 3-4 weeks after completion of chemotherapy, and at 6, 12, 18, and 24 months. Patients are followed every 2 months for 2 years after the completion of chemotherapy and then every 3 months thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 372 patients (186 per treatment arm) will be accrued for this study.

Official Title
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A Phase III Randomized, Double Blind, Placebo Controlled Trial Of Carboplatin/Etoposide With Or Without Thalidomide In Small Cell Lung Cancer (Study 12)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin, etoposide & thalidomide
* Drug: Carboplatin, etoposide & placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Limited or extensive stage disease No symptomatic brain metastases requiring immediate radiotherapy PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-3 Life expectancy At least 8 weeks Hematopoietic Not specified Hepatic Not specified Renal Ethylenediamine tetraacetic acid (EDTA) clearance greater than 60 mL/min OR Creatinine clearance greater than 50 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 effective methods of contraception (including 1 highly effective method and 1 barrier method) during and for 4 weeks after study completion No other prior malignancy within the past 3 years except nonmelanoma skin cancer or early cervical cancer No significant medical condition or laboratory finding that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior radiotherapy Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active arm (thalidomide)<br>Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral thalidomide daily beginning on day 1 for up to 24 months. | Drug: Carboplatin, etoposide & thalidomide<br>* Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral thalidomide daily beginning on day 1 for up to 24 months.<br>|
| Placebo Comparator: Placebo arm<br>Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral placebo daily beginning on day 1 for up to 24 months. | Drug: Carboplatin, etoposide & placebo<br>* Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral placebo daily beginning on day 1 for up to 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 2 years after study randomization |  | 0-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression 2 years after study randomization |  | 0-2 years | 
| Toxicity as measured by NCIC CTC 3 times weekly while undergoing chemotherapy, then monthly thereafter |  | Till end of treatment | 
| Response rates as measured by RECIST during each visit while undergoing chemotherapy and after completion of study treatment |  | Till progression | 
| Quality of life as measured by EORTC QLQ-30 and lung-specific questionnaire(LC14) at baseline, after each course, and after completion of study treatment, and at 6, 12, 18, and 24 months after day 1 of course 1 |  | 0-24 months | 
| Biological markers (measurement of VEGF, bFGF, TNF alpha, and IL-6) |  | Before treatment courses 1 and 4, and then at 9 and 18 months | 

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