Vaccine therapy for metastatic solid tumors

Inclusion Criteria:

Inclusion Criteria for Extension and Expansion Cohorts

1. For the extension cohort to be conducted at the IUSCCC (N=12), patients with histologically documented metastatic or unresectable breast or esophageal cancer will be enrolled.
2. For the expansion cohort (N=30), patients with either histologically documented metastatic or unresectable breast cancer (N=15), or histologically documented metastatic or unresectable esophageal cancer (N=15) be enrolled. All patients enrolled to this cohort are required to have measurable disease.

   Note: Measurable disease is defined as ≥ 1 lesions that can be accurately measured in ≥ 1 dimensions as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan.

   Inclusion Criteria for all Cohorts:
3. Patients must have received or refused first line standard systemic therapy for their metastatic/advanced disease.

   1. Patients with histologically confirmed esophageal cancers must have received no more than two prior cytotoxic chemotherapy regimens in the last two years.
   2. Patients with histologically confirmed breast cancers must have received no more than three prior cytotoxic chemotherapy regimens in the last two years.
4. Patients are required to have HER-2 (IHC 1+, 2+ and 3+) or EGFR over-expression (FISH and IHC) to be enrolled on this study.

   1. If the patient has had HER-2 expression measured prior to enrollment, the report alone will be accepted on the expansion phase of the study.
   2. If the patient has had EGFR expression measured prior to enrollment, the report alone will be accepted on the dose escalation phase of the study.
   3. If the patient has not had HER-2 or EGFR expression measured prior to enrollment on this study, it would be obligatory for the patient to have the tests performed to justify their status. Any clinically approved assay is acceptable. The test can be done at IUSCCC or other CLIA-certified facility.
5. Patients with prior history of treated brain metastases who are off steroids and have stable metastatic brain disease for at least 3 months are eligible.
6. Patients must be ambulatory with ECOG performance status 0, 1, or 2 (appendix II).
7. Patients must have adequate organ function as defined by:

   1. ANC ≥ 1,000/mm³, platelet count \> 700,000/mm³.
   2. Serum bilirubin \< 1.5 mg%, regardless of whether patients have liver involvement secondary to tumor. ALT must be \< 3 times upper limit of normal.
   3. Creatinine \<1.5 mg/dl or calculated creatinine clearance \> 60 ml/min
8. Patients must be at least 3 weeks past any prior surgery, cytotoxic, chemotherapy, other immunotherapy, hormonal therapy, or radiation therapy. Patients having been treated with monoclonal antibodies may enter the trial after a specified period of time (2 times the mean half life of the agent). Patients must have recovered (grade 1 or less) from any clinically significant toxicity of prior therapy prior to enrolling on study except for neuropathy where patients need to recover to grade 2 better.

   a. Patients with hormone receptor positive breast cancer who are on stable endocrine therapy are eligible if their tumor has some expression of HER-2 based on IHC of 1+ or 2+.
9. Patients must be at least 18 years of age.
10. Women of child-bearing potential must not be pregnant and must have a negative pregnancy test (Women of childbearing potential definition: (ECOG definition)).
11. Men and women of childbearing potential must agree to practice effective contraception while on this study.
12. Patients must obtain a base line Echocardiogram or MUGA and require the left ventricular ejection fraction to be within normal limits (or 50% or higher).
13. Ability to understand and the willingness to sign a written informed consent document. The patient must be aware that his/her disease is neoplastic in nature and willingly consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.
14. Patients with a history of measles vaccination or infection. a. Patients with no measles vaccination history are eligible. Note: For patients with a history of measles vaccination or infection, they will be monitored for an hour during the skin test for hypersensitivity.

Exclusion Criteria:

1. Patients with tumors that are negative for HER-2 expression based on IHC of 0 AND Fluorescence in-situ hybridization showing lack of HER-2 amplification based on most recent ASCO/CAP guidelines; or are under-expressing EGFR based on FISH and IHC.
2. Patients on targeted therapies, such as Cycline Dependent Kinase (CDK) 4/6 or mammalian target of rapamycin (mTOR) inhibitors in combination with endocrine therapy.
3. Patients who are {MVF-HER-2(266-296) and MVF-HER-2 (597-626)} immediate hypersensitivity skin test positive.
4. Patients who have evidence of active infection that requires parenteral antibiotic therapy.
5. Patients with known active HIV, hepatitis A, hepatitis B, or hepatitis C infection.
6. Patients with serious uncontrolled cardiopulmonary disorders, including congestive heart failure, symptomatic coronary artery disease, serious cardiac arrhythmia, and symptomatic chronic obstructive pulmonary disease or patients with other serious uncontrolled medical diseases. At the discretion of the treating physician, patients who show disease control for at least 6 months may be enrolled.
7. Patients who require or likely to require corticosteroids or other immunosuppressives for intercurrent disease are NOT eligible.
8. Splenectomized patients.
9. Patients with active autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis dermato-myositis, or a vasculitic syndrome.

   Note: At the discretion of the treating physician, patients who show disease control for at least 6 months may be enrolled.
10. Patients who have developed anaphylactic responses to other vaccines.

Inclusion of Women and Minorities Both men and women and members of all races and ethnic groups are eligible for this trial. Our estimates for enrollment on the clinical trial are based on a total sample size of 42 patients, assuming that the study enrolls the full complement of 12 patients in the extension phase, and an additional 15 in each of the three disease-specific subgroups as part of the expansion phase of the trial.