Marimastat Following Chemotherapy in Treating Patients With Small Cell Lung Cancer

A Phase III Study of Marimastat in Patients With Small Cell Lung Cancer Following a Response to First Line Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: marimastat; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 555
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 3G6
      • Penticton Regional Hospital
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency
    • Victoria, British Columbia, Canada, V8R 6V5
      • British Columbia Cancer Agency - Vancouver Island Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6ZB
      • Moncton Hospital
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Doctor Leon Richard Oncology Centre
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Newfoundland Cancer Treatment and Research Foundation
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • Brampton, Ontario, Canada, L6W 2Z8
      • William Osler Health Centre
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Regional Cancer Centre
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Centre
    • Mississauga, Ontario, Canada, L5M 2N1
      • Credit Valley Hospital
    • Newmarket, Ontario, Canada, L3Y 2P9
      • York County Hospital
    • North York, Ontario, Canada, M2E 1K1
      • North York General Hospital, Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre - General Campus
    • Peterborough, Ontario, Canada, K9H 7B6
      • Peterborough Oncology Clinic
    • St. Catharines, Ontario, Canada, L2R 5K3
      • Hotel Dieu Health Sciences Hospital - Niagara
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre, Sudbury
    • Thunder Bay, Ontario, Canada, P7A 7T1
      • Northwestern Ontario Regional Cancer Centre, Thunder Bay
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital - Toronto
    • Toronto, Ontario, Canada, M6R 1B5
      • Saint Joseph's Health Centre - Toronto
    • Weston, Ontario, Canada, M9N 1N8
      • Humber River Regional Hospital
    • Windsor, Ontario, Canada, N8W 2X3
      • Cancer Care Ontario - Windsor Regional Cancer Centre
  • Quebec
    • Fleurimont, Quebec, Canada, J1H 5N4
      • CHUS-Hopital Fleurimont
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H2L-4M1
      • Centre Hospitalier de l'Universite de Montreal
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrament, Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • L'Hopital Laval
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 118 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Marmistat; 10 mg PO BID	Drug: marimastat; 10 mg PO BID
Placebo Comparator: Placebo; 10 mg PO BID	Drug: Placebo; 10 mg PO BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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).	4 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Frances A. Shepherd, MD, Princess Margaret Hospital, Canada

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 1997
• Primary Completion (Actual): February 13, 2001
• Study Completion (Actual): December 15, 2008

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: February 13, 2004
• First Posted (Estimate): February 16, 2004

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: April 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: recurrent small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Marimastat
• Other Study ID Numbers: BR12; EORTC-08962 (Other Identifier: EORTC); CAN-NCIC-BR12 (Registry Identifier: PDQ registration number); CDR0000065589 (Registry Identifier: PDQ registration number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No