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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

OBJECTIVES:

Primary - Compare the survival of patients with small cell lung cancer treated with etoposide 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 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.

Blood and urine samples are collected 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 1,300 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: carboplatin
• Drug: cisplatin
• Drug: etoposide
• Drug: pravastatin
• Procedure: gene expression analysis
• Procedure: laboratory biomarker analysis
• Procedure: protein expression analysis

Primary Measures

• Survival
  • Safety Issue?: No

Secondary Measures

• Progression-free survival
  • Safety Issue?: No
• Local progression-free survival (local control)
  • Safety Issue?: No
• Response rate as measured by RECIST criteria after course 3
  • Safety Issue?: No
• Toxicity as measured by CTCAE version 3.0
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer
• Limited stage or extensive stage disease
• 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 > 10.0 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 < 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 study treatment
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University College London Hospitals

Overall Clinical Trial Officials and Contacts

Michael J. Seckl, MD, PhD Study Chair Charing Cross Hospital  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00433498

Study ID Number: CDR0000531141

ClinicalTrials.gov Identifier: NCT00433498

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database