Clinical trial NCT00003011: Marimastat Following Chemotherapy in Treating Patients With Small Cell Lung Cancer
Official title: A Phase III Study of Marimastat in Patients With Small Cell Lung Cancer Following a Response to First Line Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: recurrent small cell lung cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2004-02-16
Enrollment: 555
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Marimastat may stop the growth of lung cancer by stopping blood flow to the tumor. It is not yet known if marimastat is an effective treatment for small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of marimastat with a placebo following chemotherapy in treating patients who have small cell lung cancer.

Detailed description: 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.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically proven small cell lung cancer Complete response (CR) or partial response (PR) following first line chemotherapy required Chest x-ray showing CR or PR required. No documented prior brain metastases

PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Effective contraception use by men or women of reproductive potential No prior malignancies within 5 years except: Adequately treated nonmelanomatous skin cancer Adequately treated carcinoma in situ of the cervix No other concurrent malignancies No prior diagnosis of breast cancer, melanoma, or hypernephroma No major medical illness that would preclude prolonged administration of marimastat or required follow up No active peptic ulceration or symptoms suggestive of this diagnosis No grade 3 or 4 musculoskeletal disorders

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: One prior induction combination chemotherapy regimen required Must be completed prior to randomization Hematologically recovered before randomization Minimum of 4 cycles required No change in regimen due to progression No chemotherapy within 28 days prior to randomization if thoracic radiation is given prior to or concurrent with chemotherapy No prior marimastat Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed Must be completed prior to randomization Last dose of radiation treatment must be within 7-14 days prior to randomization if thoracic radiation and/or prophylactic cranial irradiation is given after completion of chemotherapy If severe esophagitis precludes administration of oral medication, randomization may be within 21 days after radiation therapy Surgery: No surgery within 2 weeks prior to randomization Prior complete resection of tumor allowed Other: No other investigational agents within 4 weeks prior to study, and none planned No concurrent coumarin anticoagulants and no coumarin anticoagulants within 4 weeks prior to randomization No concurrent antitumor treatment

Primary outcomes:
measure: Overall Survival
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Penticton
country: Canada
facility: Penticton Regional Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Victoria
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Moncton
country: Canada
facility: Doctor Leon Richard Oncology Centre
state: New Brunswick
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Brampton
country: Canada
facility: William Osler Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Newmarket
country: Canada
facility: York County Hospital
state: Ontario
city: North York
country: Canada
facility: North York General Hospital, Ontario
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre - General Campus
state: Ontario
city: Peterborough
country: Canada
facility: Peterborough Oncology Clinic
state: Ontario
city: St. Catharines
country: Canada
facility: Hotel Dieu Health Sciences Hospital - Niagara
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre, Sudbury
state: Ontario
city: Thunder Bay
country: Canada
facility: Northwestern Ontario Regional Cancer Centre, Thunder Bay
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Saint Joseph's Health Centre - Toronto
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital
state: Ontario
city: Windsor
country: Canada
facility: Cancer Care Ontario - Windsor Regional Cancer Centre
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint-Sacrament, Quebec
state: Quebec
city: Ste-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Free University Medical Center
name: Giuseppe Giaccone, MD, PhD
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital, Canada
name: Frances A. Shepherd, MD
role: STUDY_CHAIR
References:
citation: Huisman C, Postmus PE, Giaccone G, Smit EF. Second-line chemotherapy and its evaluation in small cell lung cancer. Cancer Treat Rev. 1999 Aug;25(4):199-206. doi: 10.1053/ctrv.1999.0125.
citation: Shepherd FA, Giaccone G, Seymour L, Debruyne C, Bezjak A, Hirsh V, Smylie M, Rubin S, Martins H, Lamont A, Krzakowski M, Sadura A, Zee B. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol. 2002 Nov 15;20(22):4434-9. doi: 10.1200/JCO.2002.02.108.