A Phase I Cancer Vaccine Study for Patients With Metastatic Breast Cancer

A Phase I Vaccine Study With Autologous Dendritic Cells Loaded With Oncofetal Antigen/iLRP in Patients With Metastatic Breast Cancer

The study uses a molecule or particle that is found only on cancer cells and is unique to cancer cells, as it is not detected on normal tissue. The molecule is known as "oncofetal antigen" or OFA. Because OFA is unique to cancer, the investigators feel OFA could be used to educate the patients' own defenses to more effectively fight the cancer on her own, he or she is harboring. Although investigators found OFA to be present in large concentrations on all cancers, it was found to be especially abundant in breast cancers. Therefore, the investigators feel that this molecule would be a good target for stimulating patient defenses especially against breast cancer cells. To accomplish this, certain defense cells (immune cells) will be washed out from the patients' blood using a machine to which the patient is connected through two small cannulas placed into veins located in the patients' arms. Those cells will be manipulated in the laboratory with artificially engineered OFA. These "reeducated" cells will be injected into the skin of patients. There will be a series of three skin injections in 4 week intervals. It is hoped that this treatment will convert the patients' defenses to a point that effective anti cancer responses will be induced. Effectiveness of the treatment will be monitored with blood tests and assessment of the size of the cancers.

The study is an open-label study to assess safety and immune responses to the universal tumor antigen OFA/iLRP. All patients will be immunized with 1 x 107 viable OFA/iLRP-loaded mature, autologous monocyte-derived dendritic cells (DCs). The DC vaccine will be administered intradermally into the proximal medial upper extremity, contralateral to the original site of breast cancer once every month for 3 months. Changes in the tumor will be documented. The patient will remain in the study unless toxicity or adverse side effects require discontinuation following RECIST and CTC guidelines, or if the patient withdraws for any other reason.

Inclusion Criteria:

• Stage IV histologically proven breast cancer as defined by the AJCC Cancer Staging Manual (6 th. Edition 2003).
• Patients must have completed one prior form of chemo and/or radiation therapy for their disease and have failed to achieve remission.
• There must be no clinical or radiographic signs of active brain metastases (CT of brain), or disease to the brain that is not considered controlled.
• At least 4 weeks must have elapsed since chemotherapy or biological therapy and 2 weeks must have elapsed since radiotherapy
• Female patients must be at least 18 years of age
• Must be ambulatory with a ECOG performance status of <2
• Must have common recall antigen DTH skin reaction >2 mm
• Must have lab values as following ANC > 1.5 x 109/L; platelets > 100 x 109/L, Hb> 9 g/dL, creatinine < 1.8 mg/dL or a creatinine clearance > 35 mL/min; total bilirubin < 2 the upper limit of normal, AST and ALT < 2.5 the upper limit of normal; albumin >2.5 g/L
• If of child bearing potential, must practice a reliable method of contraception at screening and must agree to continue this status until 6 months after receiving the last study vaccine injection. An HCG (pregnancy) test will be done monthly until the 3 vaccinations are complete.
• Signed informed consent (see Appendix A, Clinical Protocol section 25.1) to be obtained according to ICH GCP guidelines before the patient is subjected to any extra diagnostic procedures performed for evaluation of eligibility for the trial.

Exclusion Criteria:

• History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or cervical cancer stage IB
• Active infection requiring continuous use of antibiotic therapy
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia
• Autoimmune disease currently treated with steroids
• Adverse reactions to vaccines such as anaphylaxis or other serious reactions, e.g. life-threatening reactions to medicine
• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis,systemic lupus erythematosus, scleroderma, polymyositis dermatomyositis, juvenile onset, insulin dependent diabetes, or a vasculitic syndrome
• Pregnancy or lactation
• Any reason why, in the opinion of the investigator, the patient should not participate
• Patients who have received cytotoxic anti-tumor therapy within 4 weeks prior to vaccination
• Patients with active hepatitis (B, C) or HIV+ individuals
• Patients with more than four different lines of chemotherapy in the metastatic setting (excluding adjuvant chemotherapy).