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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT00433498
First received: February 8, 2007
Last updated: January 15, 2013
Last verified: January 2013
  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 phosphate
Drug: pravastatin sodium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Survival [ Time Frame: Reported at death. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time until the date of disease progression ] [ Designated as safety issue: No ]
  • Local progression-free survival (local control) [ Time Frame: Time until the date of disease progression ] [ Designated as safety issue: No ]
  • Response rate as measured by RECIST criteria after course 3 [ Time Frame: Post chemo cycle 3 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 842
Study Start Date: January 2007
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carboplatin/cisplatin and Etoposide with Pravastatin 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
Placebo Comparator: Carboplatin/cisplatin and Etoposide with Placebo 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.

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.

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 86 Study Locations
Sponsors and Collaborators
University College, London
Investigators
Study Chair: Michael J. Seckl, MD, PhD Charing Cross Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00433498     History of Changes
Other Study ID Numbers: CDR0000531141, CRUK-LUNGSTAR, EU-20649, ISRCTN56306957, EUDRACT-2005-005821-71, UCL-BRD/05/129, MREC-06-MRE10-28, CTA-20363-0215-001, CTAAC-C1312-A5335, CTAAC-C1312-A12462
Study First Received: February 8, 2007
Last Updated: January 15, 2013
Health Authority: UK: MHRA, UK: MREC

Keywords provided by University College, London:
extensive stage small cell lung cancer
limited stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Cisplatin
Carboplatin
Etoposide
Pravastatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014