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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: carboplatin
  • Should be given according to local practice but suggested doses and schedules are provided in the protocol.
• Drug: cisplatin
  • Should be given according to local practice but suggested doses and schedules are provided in the protocol.
• Drug: etoposide phosphate
  • 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.
• Drug: pravastatin sodium
  • 40mg daily oral tablet taken for a maximum of 2 years

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Carboplatin/cisplatin and Etoposide with Pravastatin
• Placebo Comparator: Carboplatin/cisplatin and Etoposide with Placebo

Primary Measures

• Survival
  • Time Frame: Reported at death.
    Safety Issue?: No

Secondary Measures

• Progression-free survival
  • Time Frame: Time until the date of disease progression
    Safety Issue?: No
• Local progression-free survival (local control)
  • Time Frame: Time until the date of disease progression
    Safety Issue?: No
• Response rate as measured by RECIST criteria after course 3
  • Time Frame: Post chemo cycle 3
    Safety Issue?: No
• Toxicity as measured by CTCAE version 3.0
  • Time Frame: At every clinic visit or if serious, an SAE form shoudl be submitted
    Safety Issue?: Yes

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

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 Investigator: University College, London Other

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 09, 2012

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

Study ID Number: CDR0000531141

ClinicalTrials.gov Identifier: NCT00433498

Health Authority: UK: MHRA, UK: MREC

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