Etoposide and Cisplatin or Carboplatin as First-Line Chemotherapy With or Without Pravastatin in Treating Patients With Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pravastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by making tumor cells more sensitive to chemotherapy. It is not yet known whether etoposide and cisplatin or carboplatin are more effective with or without pravastatin in treating small cell lung cancer. PURPOSE: This randomized phase III trial is studying etoposide and cisplatin or carboplatin to see how well they work when given as first-line chemotherapy together with pravastatin compared with first-line chemotherapy and a placebo in treating patients with small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the survival of patients with small cell lung cancer treated with etoposide phosphate in combination with cisplatin or carboplatin as first-line chemotherapy with vs without pravastatin. Secondary Compare the progression-free survival of patients treated with these regimens. Compare the local progression-free survival (local control) of these patients. Compare the response rate in these patients. Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (limited stage vs extensive stage), ECOG performance status (0 or 1 vs 2 or 3), and participating site. Patients are randomized to 1 of 2 treatment arms. All patients receive chemotherapy comprising cisplatin IV or carboplatin IV on day 1 and etoposide phosphate IV on days 1-3 or orally twice daily on days 2 and 3. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm I: Patients receive oral pravastatin daily beginning on day 1 of chemotherapy and continuing for up to 24 months. Arm II: Patients receive oral placebo daily beginning on day 1 of chemotherapy and continuing for up to 24 months. Some patients may undergo blood and urine sample collection at baseline and periodically during and after study treatment. Samples are examined by genetic analysis, metabonomics and proteomics (to detect expression of RAS proteins, phospho-Erk, and other signals downstream of RAS), and cholesterol measurements. After completion of study treatment, patients are followed every 2 months for 1 year and every 3 months thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK. PROJECTED ACCRUAL: A total of 842 patients will be accrued for this study.

Official Title
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A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: cisplatin
* Drug: etoposide phosphate
* Drug: pravastatin sodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Limited stage or extensive stage disease No mixed cell histology No symptomatic brain metastases that require immediate radiotherapy PATIENT CHARACTERISTICS: ECOG performance status 0-3 Life expectancy > 8 weeks Platelet count > 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count > 1,500/mm^3 Glomerular filtration rate ≥ 50 mL/min Creatine kinase ≤ 5 times upper limit of normal (ULN) Liver function tests (ALP, ALT/AST, and bilirubin) < 3 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 1 year after completion of chemotherapy/radiotherapy and for an additional 28 days after completion of pravastatin sodium Able to tolerate chemotherapy No evidence of significant medical condition or laboratory finding that, in the opinion of the investigator, would preclude study participation No family history of hypercholesterolemia No history of malignant tumor unless the patient has been without evidence of disease for ≥ 3 years or tumor was a nonmelanoma skin tumor or early cervical cancer PRIOR CONCURRENT THERAPY: More than 12 months since prior statin More than 4 weeks since prior fibrates (e.g., bezofibrate, gemfibrozil, or fenofibrate) No prior chemotherapy for this cancer No prior radiotherapy for this cancer unless to distant metastases (i.e., not within the thorax or thoracic/cervical spine area) No concurrent cyclosporine Concurrent radiotherapy allowed

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: Carboplatin/cisplatin and Etoposide with Pravastatin<br> | Drug: carboplatin<br>* Should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>Drug: cisplatin<br>* Should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>Drug: etoposide phosphate<br>* Day 1: given by IV, days 2 and 3 given by IV or oral. Dose should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>Drug: pravastatin sodium<br>* 40mg daily oral tablet taken for a maximum of 2 years<br>|
| Placebo Comparator: Carboplatin/cisplatin and Etoposide with Placebo<br> | Drug: carboplatin<br>* Should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>Drug: cisplatin<br>* Should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>Drug: etoposide phosphate<br>* Day 1: given by IV, days 2 and 3 given by IV or oral. Dose should be given according to local practice but suggested doses and schedules are provided in the protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Reported at death. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Time until the date of disease progression | 
| Local progression-free survival (local control) |  | Time until the date of disease progression | 
| Response rate as measured by RECIST criteria after course 3 |  | Post chemo cycle 3 | 
| Toxicity as measured by CTCAE version 3.0 |  | At every clinic visit or if serious, an SAE form shoudl be submitted | 

 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