Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Biomarker/Laboratory analysis, Treatment	Active	18 and over	Other	CRUK-LUNGSTAR EU-20649, ISRCTN56306957, EUDRACT-2005-005821-71, UCL-BRD/05/129, NCT00433498

Objectives

Primary

1. 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

1. Compare the progression-free survival of patients treated with these regimens.
2. Compare the local progression-free survival (local control) of these patients.
3. Compare the response rate in these patients.
4. Compare the toxicity of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed small cell lung cancer
  • Limited stage or extensive stage disease



• No symptomatic brain metastases that require immediate radiotherapy

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

Patient Characteristics:

• ECOG performance status 0-3
• Life expectancy > 8 weeks
• Platelet count > 100,000/mm³
• Hemoglobin > 10.0 g/dL
• Absolute neutrophil count > 1,500/mm³
• 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

Expected Enrollment

A total of 1,300 patients will be accrued for this study.

Outcomes

Survival

Progression-free survival
Local progression-free survival (local control)
Response rate as measured by RECIST criteria after course 3
Toxicity as measured by CTCAE version 3.0

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.

Trial Contact Information

Trial Lead Organizations

University College Hospital - London

Michael Seckl, MD, PhD, Protocol chair		Ph: 44-20-8846-1421

United Kingdom
England
	London
	Charing Cross Hospital
		Michael Seckl, MD, PhD	Ph:  44-20-8846-1421
	Newport
	St. Mary's Hospital
		Christopher Baughan, MD	Ph:  44-1983-524-081
	Southampton
	Southampton General Hospital
		Christian Ottensmeier, MD, PhD	Ph:  44-23-8079-6184
			Email: cho@soton.ac.uk

Registry Information
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
Trial Start Date		2006-10-01
Registered in ClinicalTrials.gov		NCT00433498
Date Submitted to PDQ		2007-01-16
Information Last Verified		2007-02-26