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

Sponsored by:	University College London Hospitals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00433498

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: carboplatin Drug: cisplatin Drug: etoposide Drug: pravastatin Genetic: gene expression analysis Genetic: protein expression analysis Other: laboratory biomarker analysis	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Etoposide Carboplatin Pravastatin Pravastatin sodium Etoposide phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]
Local progression-free survival (local control) [ Designated as safety issue: No ]
Response rate as measured by RECIST criteria after course 3 [ Designated as safety issue: No ]
Toxicity as measured by CTCAE version 3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	1300
Study Start Date:	October 2006

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433498

Locations

United Kingdom, England
Charing Cross Hospital	Recruiting
London, England, United Kingdom, W6 8RF
Contact: Michael J. Seckl, MD, PhD 44-20-8846-1421
Southampton General Hospital	Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Christian Ottensmeier, MD, PhD 44-23-8079-6184 cho@soton.ac.uk
St. Mary's Hospital	Recruiting
Newport, England, United Kingdom, PO30 5TG
Contact: Christopher Baughan, MD 44-1983-524-081

Sponsors and Collaborators

University College London Hospitals

Investigators

Study Chair:

Michael J. Seckl, MD, PhD

Charing Cross Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000531141, CRUK-LUNGSTAR, EU-20649, ISRCTN56306957, EUDRACT-2005-005821-71, UCL-BRD/05/129
Study First Received:	February 8, 2007
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00433498 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

extensive stage small cell lung cancer
limited stage small cell lung cancer

Study placed in the following topic categories:

Antimetabolites
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Antilipemic Agents
Anticholesteremic Agents
Carboplatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Etoposide phosphate
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
Pravastatin

Neuroectodermal Tumors
Radiation-Sensitizing Agents
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Etoposide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Carcinoma, Neuroendocrine
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Pravastatin
Neoplasms by Site
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Etoposide

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents
Carboplatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Neuroendocrine Tumors
Carcinoma
Carcinoma, Small Cell
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases

ClinicalTrials.gov processed this record on September 02, 2009