Vaccine Therapy in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Biological: recombinant vaccinia-MUC1 vaccine
* Biological: recombinant vaccinia-TRICOM vaccine
* Other: laboratory biomarker analysis
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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 Subjects must not have undergone splenectomy The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least three weeks after vaccination, their close household contacts: persons with active or a history of extensive eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves; pregnant or nursing women; children under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection; close household contacts are those who share housing or have close physical contact; determination of the severity of these conditions will be made by the investigator or co-investigator Subjects must not have any other serious medical condition that in the opinion of the investigator is incompatible with the protocol; subjects with active infections requiring antibiotics are not eligible until the infection has cleared and the antibiotics have been stopped for at least 3 days Subjects must have had prior vaccinia (smallpox) exposure, determined by subject history, medical documentation, or scar characteristic of vaccinia exposure; there must be no history of allergy or untoward reaction to prior vaccinia (smallpox) vaccination Tumor tissue positive for staining with MAbs DF3 and/or DF3-P or elevated serum CA15-3 (also known as CA27-29); note: this can be done on stored slides, but subject will be responsible for costs if not covered by insurance Subjects must not have a history of seizures, encephalitis or multiple sclerosis Subjects must not be allergic to eggs Women of child-bearing potential must agree to use highly effective contraception or abstinence prior to study entry and for at least 4 weeks after the last vaccination; women who are breast-feeding are not eligible for this study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Signed informed consent Participants who have been previously treated with vaccinia vectors or MUC1 such as those on protocol T98-0057 (DFPCC # 97-050) are not eligible for this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (vaccine therapy)<br>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. | Biological: recombinant vaccinia-MUC1 vaccine<br>* Given intradermally<br>* Other names: vaccinia-MUC-1 vaccine;Biological: recombinant vaccinia-TRICOM vaccine<br>* Given intradermally<br>* Other names: Vaccinia-TRICOM;Other: laboratory biomarker analysis<br>* Correlative studies<br>Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 4 weeks |