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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Male Breast Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- MTD defined as the dose level preceding the dose in which 2 out of 6 patients experience dose limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria version 2.0
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
Vaccines may make the body build an immune response to kill tumor cells. This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic breast cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the toxicity associated with repeated vaccination with an admixture of recombinant vaccinia viruses (rV-MUC-1 and rV-TRICOM). II. To determine the maximum tolerated dose (MTD) of rV-MUC-1 and rV-TRICOM vaccine admixture. III. To evaluate the toxicity of adding GM-CSF to the admixture of the rV-MUC-1 and rV-TRICOM. SECONDARY OBJECTIVES: I. To assess host immune reactivity following rV-MUC-1 and rV-TRICOM with and without GM-CSF administration. II. To determine whether vaccination with rV-MUC-1 and rV-TRICOM with and without GM-CSF is associated with antitumor activity. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must have a histologically confirmed diagnosis of metastatic carcinoma of the breast; measurable disease is not required; subjects who are NED are eligible; subjects must have had at least one prior regimen of chemotherapy, immunotherapy, or hormonal therapy prior to entering this study; subjects may have received any number of prior therapies for metastatic disease
- •Subjects must have an ECOG performance status of 0-1
- •WBC \> 2000/mm\^3
- •Platelet count \> 100,000/mm\^3
- •Serum creatinine =\< 2.0 mg/dl
- •Serum bilirubin =\< 1.5 mg/dl
- •SGPT \< 3 times the upper limit of normal
- •\>= 4 weeks since chemotherapy (\>= 6 weeks for nitrosoureas or mitomycin C), hormonal therapy or radiation therapy; subjects must have recovered from all acute toxicity associated with the prior regimen; subjects receiving concurrent hormonal treatment or local radiation are not eligible
- •Subjects must be HLA typed if not already previously done (5/10 subjects at the MTD dose level must be HLA A2 positive)
- •Subjects must not have clinical evidence of altered immune responsiveness or autoimmune syndromes (scleroderma, systemic lupus erythematosus, etc.); subjects must be HIV antibody negative; this treatment may be associated with increased adverse effects for individuals with immune deficiencies, and HIV-associated symptoms preclude accurate assessment of toxicity
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
MTD defined as the dose level preceding the dose in which 2 out of 6 patients experience dose limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria version 2.0
Time Frame: 4 weeks