Vaccine Therapy in Treating Patients With Metastatic Breast Cancer
Vaccine Therapy in Treating Patients With Metastatic Breast Cancer
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.
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.
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