A Phase III Study of Marimastat in Patients With Small Cell Lung Cancer Following a Response to First Line Chemotherapy
OBJECTIVES: I. Determine whether treatment with the oral matrix metalloproteinase inhibitor
(MMPI) marimastat prolongs overall survival and time to progression in patients with small
cell lung cancer who have achieved complete or partial remission after first line
chemotherapy, with or without radiotherapy. II. Determine the tolerability and toxicity of
prolonged administration of marimastat in patients with small cell lung cancer. III.
Determine the effect of prolonged administration of marimastat on the quality of life of
patients with small cell lung cancer.
OUTLINE: This is a randomized, double blind, multicenter, placebo controlled study. Patients
are stratified by stage of disease at diagnosis, response to prior
chemotherapy/radiotherapy, type of thoracic radiotherapy, and cooperative group. Patients
are randomized into two groups. Half of the patients take marimastat orally twice a day
(breakfast and evening meal); the other half take placebo orally twice a day (breakfast and
evening meal). Treatment continues for 2 years or until documented disease recurrence or
progression and institution of further anticancer treatment, occurrence of unacceptable
toxicity, initiation of anticoagulant treatment, or development of intercurrent illness. All
patients are followed every 6 months until death.
PROJECTED ACCRUAL: The planned sample size is 360, with an equal number of patients in both
arms, accrued at a rate of 240 responders per year (resulting in an accrual period of
approximately 1.5 years). The total duration of the study is estimated as 2.3 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
To determine whether treatment with the oral metalloproteinase inhibitor marimastat prolongs overall survival and time to progression in patients with small cell lung cancer who have achieved complete or partial remission after first line chemotherapy (+I- radiotherapy).
Giuseppe Giaccone, MD, PhD
Free University Medical Center
Canada: Health Canada