A Dose-escalation Vaccine Trial in HER2-overexpressing Patients With High-risk Breast Cancer
A Dose-escalation Vaccine Trial in HER2-overexpressing Patients With High-risk Breast Cancer
Treatment phase:

 The purpose of this study is to evaluate the safety and the immune response elicited by a new
 anti-cancer therapy in patients with breast cancer in remission but who are at high risk of
 relapse. The study product is an immunotherapeutic consisting of the recombinant dHER2
 protein combined with an immunostimulant called AS15. The study aims to determine the optimal
 of three different dose levels of dHER2 combined with the same fixed dose of AS15 by
 assessing the safety and the immune response elicited after a series of injections of the
 study product.

 Five-year follow-up phase:

 This part of the study aims to assess any late onset toxicity of the study treatment through
 yearly follow-up visits and to monitor the patients' survival and disease status up to five
 years after the last administration of the study treatment. The patients' immune response is
 also measured to assess the robustness of the immune response elicited by the study
 treatment.
Inclusion criteria:

 1. Patient must have a previous diagnosis of HER2/neu-positive breast cancer: FISH
 positive test (for HercepTest 2+ patients), or, HercepTest 3+ patients.

 2. Patients must be Stage II with at least one positive node or Stage III in remission.
 Patients must have had standard treatment for their cancer, including lymph node
 dissection and at least one course of standard adjuvant treatment.

 3. Patient must have completed at least one course of standard adjuvant treatment within
 5 years of study entry.

 4. Patient may be on concurrent hormonal therapy.

 5. Patient must be free of recurrent breast cancer as shown by standard diagnostic tests
 at entry onto study.

 6. Patient must have a chest X-ray showing no evidence of disease.

 7. Patient should have an expected survival of at least 12 months.

 8. Written informed consent must be obtained prior to any protocol-specific procedures
 being performed.

 9. Patient must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0.

 10. Patient must not be pregnant and must use adequate contraception throughout the study
 and must plan to not bear children in the future.

 11. Patient must not be lactating.

 12. Patient must have a negative pregnancy test prior to enrollment. Pregnancy testing
 need not be done for patients who are > 55 years of age, post-menopausal or surgically
 sterile.

 13. Patient must be 40 to 70 years of age inclusive. Patients younger than 40 years of age
 may be enrolled if they are sterile and incapable of childbearing.
 Chemotherapy-induced amenorrhea is not considered to be a sign of sterility.

 14. Patient must have adequate bone marrow reserve as indicated by: WBC ≥3000/mm3,
 neutrophils ≥1500/ mm3, platelets ≥100,000 mm3, lymphocytes ≥1000/mm3, and hemoglobin
 ≥10.0 g/dL.

 15. Patient must have an absolute CD4 cell count of >200 cells/mm3.

 16. Patient must have adequate renal function.

 17. Patient must have adequate hepatic function as indicated by: serum bilirubin within
 normal limits, aspartate aminotransferase <1.5 times the upper limit of normal and an
 alkaline phosphatase <1.2 times the upper limit of normal. Patients with an alkaline
 phosphatase above normal must have negative bone scans and abdominal CT scans prior to
 entry onto protocol.

 18. Patient must have a baseline left ventricular ejection fraction (LVEF) measured by
 multi-gated acquisition (MUGA) scan equal to or greater than the lower limit of normal
 for the radiology facility. The serial MUGA scans for each individual must also be
 performed at the same radiology facility, using the same equipment in the same manner,
 for consistency of method.

 19. Patients who had an earlier baseline MUGA scan at the radiological facility of the
 investigator's site to be used in the study, such as a MUGA scan done prior to
 adjuvant treatment, must meet the above criteria for LVEF AND must also not have had a
 decrease in LVEF of above 15 percentage points from the original baseline MUGA scan.
 Patients who have not had a MUGA scan done at this radiological facility prior to
 adjuvant treatment must have a normal MUGA scan at screening.

 20. Patient must not be known to be HIV positive. Results of virology screening must
 indicate that the patient has negative serology for HCV (hepatitis C virus) and is
 negative for HBsAg (hepatitis B surface antigen). (HBV testing indicating positive
 serology (antibodies) is allowed.)

 Exclusion criteria:

 1. Patients who are presently being treated with Herceptin or have been treated with
 Herceptin in the past.

 2. Patients who have received surgery or chemotherapy treatments within 8 weeks prior to
 enrollment. Patients who have received radiation therapy within 12 weeks prior to
 enrollment.

 3. Patients who have received > 300 mg/m2 doxorubicin (cumulative dose) or > 600 mg/m2
 epirubicin (cumulative dose).

 4. Patients with any uncontrolled bleeding disorder or coagulation disorder or
 thrombocytopenia or prothrombotic disorder.

 5. Patients with auto-immune disease such as, but not limited to multiple sclerosis,
 lupus, and inflammatory bowel disease, Graves' disease and Hashimoto's disease.

 6. Patients with a history of previous anaphylaxis or severe allergic reaction to
 vaccines or unknown allergens.

 7. Patients with previous splenectomy or radiation to the spleen.

 8. Patients who have received a major organ graft (including bone-marrow
 transplantation).

 9. Patients who require chronic oral treatment (defined as more than 14 days) with
 immunosuppressive agents including glucocorticosteroids or other immune-modifying
 drugs.

 10. Previous or concomitant malignancies at other sites, except effectively treated
 non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated
 malignancy that has been in remission for > 2 years and highly likely to have been
 cured.

 11. Concurrent severe medical problems unrelated to the malignancy, which would
 significantly limit full compliance with the study or expose the patient to
 unacceptable risk.

 12. Patients with previous congestive heart failure or difficult-to-control hypertension.
 Patients with known coronary artery disease, arrhythmia requiring treatment,
 clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular
 hypertrophy on electrocardiogram (EKG) or previous myocardial infarction.

 13. Patients with psychiatric or addictive disorders that may compromise the ability to
 give informed consent, or comply with the trial procedures.

 14. Patients who have received any investigational or non-registered drug or
 non-registered vaccine other than the study product within the 30 days preceding the
 first dose of study product, or who plan to receive such a drug during the study
 period.

 15. Patients who have received any immunoglobulins and/or blood products within the 3
 weeks prior to study product administration.

 16. Patients who have received any commercial vaccine within one week before the first
 dose of the study product.