Marimastat or No Further Therapy in Treating Women With Metastatic Breast Cancer That Is Responding or Stable Following Chemotherapy

Breast Cancer Clinical Trial

Official title:

A Randomized Phase III Trial of Marimastat Versus Placebo in Patients With Metastatic Breast Cancer Who Have Responding or Stable Disease After Induction Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003010
• Other study ID #: CDR0000065585
• Secondary ID: E2196NCCTG-E2196
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 1997

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Marimastat may stop the growth of breast cancer by stopping blood flow to the tumor. It is not known whether chemotherapy is more effective with or without marimastat for breast cancer.

PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of marimastat with that of no further therapy in treating women who have metastatic breast cancer that is responding or stable after chemotherapy.

Description:

OBJECTIVES: I. Determine whether marimastat prolongs progression-free survival in women with metastatic breast cancer who have responding or stable disease after receiving standard systemic chemotherapy. II. Determine the toxic effects of marimastat compared with placebo in patients with metastatic breast cancer who have responding or stable disease after receiving standard systemic chemotherapy. III. Determine whether there is an association between trough marimastat concentration and time to disease progression and toxicity.

OUTLINE: This is a randomized, double blind, placebo controlled study. Patients are stratified by the number of involved disease sites at study entry, prior chemotherapy for metastases, osseous disease only at study entry, and bisphosphonate therapy at study entry, and concurrent hormonal therapy (yes vs no). Patients are randomized into two groups. Patients take either marimastat or placebo, one capsule orally twice a day, approximately every 12 hours (i.e., during or after breakfast and dinner). The drug or placebo is given until the development of progressive disease or prohibitive toxicity.

PROJECTED ACCRUAL: A total of 334 patients will be accrued for this study over 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast with previous manifestations of progressing regional or metastatic cancer Received one prior systemic chemotherapy regimen for the treatment of metastases, which meets all of the following criteria: Included either doxorubicin, a taxane (i.e., paclitaxel or docetaxel), or both 6-8 courses were given If weekly taxane therapy received, at least 12 doses were given Recovered from all related toxic effects (except alopecia and/or neuropathy) 3-6 weeks have elapsed since last course of chemotherapy was given No more than 40 weeks have elapsed since the first dose of chemotherapy for metastases No current or prior history of brain metastases Responding or stable disease since the initiation of systemic chemotherapy (i.e., no disease progression) required No prior enrollment on ECOG trials for metastatic disease

PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal Status: Not specified Performance status: ECOG 0 or 1 Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater 2 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test required if pre- or peri-menopausal (i.e., last menstrual period within one year prior to study) Pre- or peri-menopausal sexually active women must use effective contraception No other invasive malignancy within last 5 years except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix No history of rheumatoid arthritis, osteoarthritis, symptomatic osteoarthritis requiring therapy, or other inflammatory arthritis At least 5 years since prior invasive malignancies except: Curatively treated basal cell or squamous cell carcinoma of the skin Carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No prior trastuzumab Chemotherapy: See Disease Characteristics No concurrent chemotherapy No prior marimastat or batimastat Endocrine therapy: Prior and/or concurrent hormonal therapy for breast cancer allowed Concurrent hormonal therapy allowed Radiotherapy: No concurrent radiotherapy Surgery: No prior organ allograft Other: At least 4 weeks since other investigational agents No concurrent bisphosphonate therapy unless it was initiated prior to the study No concurrent immunosuppressive therapy Patients receiving anticoagulant therapy must be carefully monitored

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• marimastat

Locations

Country	Name	City	State
United States	Medcenter One Health System	Bismarck	North Dakota
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey
United States	Hunterdon Regional Cancer Center	Flemington	New Jersey
United States	Altru Health Systems	Grand Forks	North Dakota
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Riverview Medical Center	Red Bank	New Jersey
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CentraCare Clinic	Saint Cloud	Minnesota
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	St. Francis Medical Center	Trenton	New Jersey
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI), North Central Cancer Treatment Group

Country where clinical trial is conducted

United States, 

References & Publications (3)

Sparano JA, Bernardo P, Gradishar WJ, et al.: Higher trough marimastat levels are associated with accelerated disease progression and worse survival: results of a randomized phase III trial comparing marimastat with placebo in metastatic breast cancer (MB

Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eas — View Citation

Zucker S, Wang M, Sparano JA, Gradishar WJ, Ingle JN, Davidson NE; Eastern Cooperative Oncology Group. Plasma matrix metalloproteinases 7 and 9 in patients with metastatic breast cancer treated with marimastat or placebo: Eastern Cooperative Oncology Grou — View Citation