| Eligibility |
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 gastrointestinal 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 gastrointestinal 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
metastases (if applicable) and patients with histologically confirmed pancreatic and
esophageal cancers must have received no more than two prior cytotoxic chemotherapy
regimens in the last two years after standard therapy. Patients with histologically
confirmed breast, and gastrointestinal cancers must have received no more than three
prior cytotoxic chemotherapy regimens in the last two years after standard therapy.
4. Progressive disease after at least one line of standard therapy.
5. Patients with pancreatic and esophageal cancers must have received no more than two
prior cytotoxic chemotherapy regimens in the last two years. Patients with breast and
gastrointestinal cancers must have received no more than three prior cytotoxic
chemotherapy regimens in the last two years.
6. 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. HER-2 status can be performed by a variety of tests.
Either IHC or FISH assay are acceptable if breast tumor tissues (previously
frozen) are available. The test can be done at OSU or elsewhere if the patient is
from out of town.
7. 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.
8. Patients must be ambulatory with an ECOG performance status 0, 1, or 2 (appendix II).
9. Patients must have adequate organ function as defined by:
1. ANC = 1,000/mm³, platelet count > 100,000/mm³.
2. Serum bilirubin < 1.5 mg%, regardless of whether patients have liver involvement
secondary to tumor. ALT must be < 2 times upper limit of normal.
3. Creatinine <1.5 mg/dl or calculated creatinine clearance > 60 ml/min
10. 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 from any
toxicity of prior therapy prior to enrolling on study except for neuropathy where
patients need to recover to less than grade 2.
1. 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+.
11. Patients must be at least 18 years of age.
12. Women of child-bearing potential must not be pregnant and must have a negative
pregnancy test (Women of childbearing potential definition: (ECOG definition)).
13. Men and women must agree to practice effective contraception while on this study.
14. 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).
15. 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.
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 antibiotic therapy.
Patients must have been off antibiotic treatment for at least 3 weeks prior to
initiating treatment and must be confirmed to be clear of the infection.
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
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