Clinical trial NCT00003752: Bexarotene in Treating Patients With Metastatic Breast Cancer
Official title: A Multicenter Phase II Evaluation of Targretin (Bexarotene) Capsules in Patients With Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-05-25
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Randomized phase II trial to study the effectiveness of bexarotene in treating patients who have metastatic breast cancer.

Detailed description: OBJECTIVES: I. Compare the efficacy of oral bexarotene (LGD1069) at two different dose levels in patients with advanced breast cancer. II. Assess the safety and tolerability of this treatment regimen in this patient population. III. Evaluate the efficacy of oral bexarotene in terms of induction of differentiation and decreased aberrant cell proliferation in these patients.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to prior therapy for metastatic disease. Patients are randomized to one of two dose levels. All patients receive oral bexarotene once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every week for the first month, at weeks 6 and 8, then monthly thereafter.

PROJECTED ACCRUAL: A total of 84-180 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast cancer No CNS metastases No rapidly progressing visceral disease Previously irradiated lesions(s) may be designated as measurable indicator tumor(s) only if more than 6 months since radiotherapy, patient has no other measurable disease regrowth, and bidimensionally measurable regrowth is documented within 2 months prior to study Stratum 1 (hormonal): Must be hormone receptor positive (ER or PR) Prior hormonal therapy only allowed for metastatic disease Must have progressed on last hormonal regimen Must have at least one bidimensionally measurable tumor Stratum 2 (chemotherapy): Hormone receptor positive or negative Must have progressed on or after prior chemotherapy (1-2 regimens) for metastatic disease (bone marrow transplant counts as 2 regimens) Prior hormonal therapy allowed Must have at least one bidimensionally measurable tumor Stratum 3 (tamoxifen): Must be hormone receptor positive (ER or PR) and progressing on tamoxifen No symptomatic visceral metastasis if on adjuvant tamoxifen at time of systemic recurrence Must have at least one bidimensionally measurable tumor, or lytic bone lesion which measures at least one cm in diameter Hormone receptor status: See above

PATIENT CHARACTERISTICS: Age: Over 18 Menopausal status: Not specified Performance status: ECOG 0-2 OR Karnofsky 60-100% Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Fasting triglycerides within normal range Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and/or SGPT no greater than 2.5 times ULN Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable Renal: Creatinine less than 2 times ULN OR Creatinine clearance greater than 40 mL/min Concurrent medication with drugs that significantly alter renal metabolism (e.g., probenecid) allowed only if dosage stable Other: At least 5 years since any other prior invasive malignancy except basal cell and squamous cell carcinoma of the skin No serious concurrent illness that would prevent compliance No history of or clinically significant risk factors for developing pancreatitis Fasting triglycerides within normal range Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior monoclonal antibody HER2 therapy for metastatic disease allowed only if combined with chemotherapy or hormonal therapy and treatment failed No concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 4 weeks since prior cytotoxic chemotherapy (at least 6 weeks since prior mitomycin or nitrosourea) No prior retinoid therapy for breast cancer At least 3 months since any other prior retinoid therapy except topical application for dermatological indications No concurrent chemotherapy Endocrine therapy: See Disease Characteristics At least 2 weeks since prior non-FDA approved hormonal therapy No other concurrent hormonal therapy except chronic low dose hormone replacement therapy or low dose corticosteroids for noncancer indication Radiotherapy: See Disease Characteristics Prior radiotherapy allowed Concurrent radiotherapy allowed only to non-indicator tumor(s) that do not represent new disease or disease progression Surgery: Prior surgery allowed Other: At least one month since prior investigational therapy (except hormonal) No other concurrent investigational therapy Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable No more than 15,000 IU of vitamin A consumed daily

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Southern California Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Vincent T. Lombardi Cancer Research Center, Georgetown University
state: District of Columbia
city: Jacksonville
country: United States
facility: Baptist Regional Cancer Institute - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Louisiana State University School of Medicine
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants Inc
state: Ohio
city: Portland
country: United States
facility: Oregon Cancer Center at Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon-Minnie Pearl Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Charlottesville
country: United States
facility: Cancer Center, University of Virginia HSC
state: Virginia
Study officials:
affiliation: Dana-Farber Cancer Institute
name: George D. Demetri, MD
role: STUDY_CHAIR
References:
citation: Esteva FJ, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, Tripathy D, Cohen R, DeMichele A, Yocum RC, Osborne CK, Hayes DF, Hortobagyi GN, Winer E, Demetri GD. Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol. 2003 Mar 15;21(6):999-1006. doi: 10.1200/JCO.2003.05.068.