A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small Lung Cancer
18 Years
N/A
Both
Lung Cancer
Trial Information
A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small 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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Survival
Outcome Time Frame:
Reported at death.
Safety Issue:
No
Principal Investigator
Michael J. Seckl, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Charing Cross Hospital
Authority:
UK: MHRA, UK: MREC
Study ID:
CDR0000531141
NCT ID:
NCT00433498
Start Date:
January 2007
Completion Date:
Related Keywords:
- Lung Cancer
- extensive stage small cell lung cancer
- limited stage small cell lung cancer
- Lung Neoplasms
- Small Cell Lung Carcinoma
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