Vaccine Therapy in Treating Patients With Metastatic Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: recombinant vaccinia-MUC-1 vaccine (Drug); recombinant vaccinia-TRICOM vaccine (Drug); sargramostim (Drug); colony-stimulating factor therapy (Procedure); non-specific immune-modulator therapy (Procedure); recombinant viral vaccine therapy (Procedure)

Phase: Phase 1

Status: Completed

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Joseph Paul Eder, MD, Principal Investigator, Affiliation: Dana-Farber Cancer Institute

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic breast cancer.

Official title: A Phase I Trial of an Admixture of Recombinant Vaccinia Virus That Express DF3/MUC1 and rV-TRICOM (B7.ICAM-1, and LFA-3) in Patients With Metastatic Adenocarcinoma of the Breast

Study design: Treatment, Open Label

Detailed description: OBJECTIVES: Primary Determine the toxicity of vaccination comprising recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine in patients with metastatic breast cancer. Determine the maximum tolerated dose of this regimen in these patients. Determine the toxicity of this regimen when administered with sargramostim (GM-CSF) in these patients. Secondary Determine the host immune reactivity in patients treated with this regimen with or without GM-CSF. Determine the antitumor activity in patients treated with this regimen with or without GM-CSF. OUTLINE: This is an open-label, dose-escalation study. Patients receive vaccination comprising recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine intradermally on days 1 and 29 (for a total of 2 doses) in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients (including 5 HLA-A2-positive patients) receive vaccination as above at the MTD and sargramostim (GM-CSF) subcutaneously on days 1-4 and 29-32. Patients are followed at 4 weeks, monthly until disease progression, and then annually for up to 15 years. PROJECTED ACCRUAL: A total of 11-22 patients will be accrued for this study within 18-24 months.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast cancer Meets 1 of the following criteria: Tumor tissue stains positive with monoclonal antibodies DF3 and/or DF3-P Elevated CA 15-3 Received at least 1 prior regimen of chemotherapy, immunotherapy, or hormonal therapy HLA status known Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Male or female Menopausal status Not specified Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic WBC greater than 2,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic Bilirubin no greater than 1. 5 mg/dL SGPT less than 3 times upper limit of normal Renal Creatinine no greater 2. 0 mg/dL Immunologic No active or prior extensive eczema or other eczematoid skin disorders No active, chronic, or exfoliative skin conditions (e. g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open wounds or rashes) No clinical evidence of altered immune responsiveness No immunodeficiency or immunosuppression by disease or therapy No autoimmune syndromes (e. g., scleroderma or systemic lupus erythematosus) No prior allergic or untoward reaction to vaccinia (smallpox) vaccination No allergy to eggs No active infection requiring antibiotics HIV negative Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 4 weeks after study participation No history of seizures, encephalitis, or multiple sclerosis Must be able to avoid close household contact with any of the following individuals for at least 3 weeks after study vaccination: Persons with active or prior extensive eczema or other eczematoid skin disorders Persons with acute, chronic, or exfoliative skin disorders Pregnant or nursing women Children under age 5 Immunodeficient or immunosuppressed persons (by disease or therapy, including HIV infection) No other concurrent serious medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Prior vaccinia (smallpox) exposure required At least 21 days since prior flu vaccination No prior vaccinia vectors or MUC1 No other concurrent anticancer biologic therapy (e. g., interferon or interleukin) Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) Endocrine therapy See Disease Characteristics At least 4 weeks since prior hormonal therapy No concurrent hormonal treatment No concurrent steroid therapy Steroid creams or inhalers allowed No concurrent dexamethasone or other steroids for antiemetic purposes Radiotherapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery No prior splenectomy Other Recovered from all prior therapy At least 3 days since prior antibiotics for active infection

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2003
Last updated: November 15, 2007