A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- carboplatin
- Conditions
- Lung Cancer
- Sponsor
- University College, London
- Enrollment
- 846
- Locations
- 86
- Primary Endpoint
- Survival
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Carboplatin/cisplatin and Etoposide with Pravastatin
Intervention: carboplatin
Carboplatin/cisplatin and Etoposide with Pravastatin
Intervention: cisplatin
Carboplatin/cisplatin and Etoposide with Pravastatin
Intervention: etoposide phosphate
Carboplatin/cisplatin and Etoposide with Pravastatin
Intervention: pravastatin sodium
Carboplatin/cisplatin and Etoposide with Placebo
Intervention: carboplatin
Carboplatin/cisplatin and Etoposide with Placebo
Intervention: cisplatin
Carboplatin/cisplatin and Etoposide with Placebo
Intervention: etoposide phosphate
Outcomes
Primary Outcomes
Survival
Time Frame: Reported at death.
Secondary Outcomes
- Response rate as measured by RECIST criteria after course 3(Post chemo cycle 3)
- Local progression-free survival (local control)(Time until the date of disease progression)
- Progression-free survival(Time until the date of disease progression)
- Toxicity as measured by CTCAE version 3.0(At every clinic visit or if serious, an SAE form shoudl be submitted)