Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Metastatic Breast Cancer Subjects

A Double-blind, Randomized Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Subjects With Metastatic Breast Cancer

The purpose of this study is to compare active immunotherapy (OPT-822/OPT-821) with PBS in combination with low dose cyclophosphamide, in post-treated metastatic breast cancer subjects with stable disease or response to treatment.

Inclusion Criteria:

• Female subjects ≥ 21 years of age with histological or cytological diagnosis of breast carcinoma.

• Subjects with metastatic breast cancer who have achieved stable disease (SD), partial response (PR), or complete response (CR) after at least 1 regimen of anticancer therapy (i.e. chemotherapy or target therapy, either alone or in any combination). Involvement of supraclavicular lymph node is considered metastasis.

• Subjects must have recovered from toxicities of prior therapies. (i.e. CTCAE ≤ grade 2).

• Performance status: ECOG ≤ 1 and life expectancy ≥ 3 months.

• Organ Function Requirements - Subjects must have adequate organ functions as defined below:

  • AST/ALT ≤ 3X ULN (upper limit of normal)
  • AST/ALT ≤ 5X ULN [with underlying Liver Metastasis]
  • Total Bilirubin ≤ 2.0 X ULN
  • Serum Creatinine ≤ 1.5X ULN
  • ANC ≥ 1500 /μL
  • Platelets > 100,000/μL
  • No Symptomatic Congestive Heart Failure (Ejection Fraction EF ≥ 50%)

• Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.

• All positive or negative ER (estrogen receptor), PR (progesterone receptor), and HER-2 subjects are eligible for this study.

• However, subjects who are HER-2 positive and responsive to anti-HER-2 therapy (e.g. Herceptin), are encouraged to remain on anti-HER-2 therapy and not enroll in this trial.

• Subjects who desire to enroll in this study and for whom anti-HER-2 therapy is not available or contraindicated, may be eligible to enroll in this trial.

• In countries where continuous anti-HER2 therapy is considered standard of care for HER-2 positive metastatic disease, HER-2 positive subjects are not eligible.

• Women of childbearing potential must be willing to implement adequate contraception during the study. An adequate method of contraception will be at the investigator's discretion.

Exclusion Criteria:

• Subjects are pregnant or breast-feeding at entry.

• Subjects with more than 2 events of disease progression after the development of metastatic breast cancer.

• Subjects who are currently receiving any other concomitant anticancer therapy with the EXCEPTION of bisphosphonates and hormone therapy.

  • During the study period, subjects using hormonal therapy and bisphosphonates should maintain a constant dose and should not change existing regimen.
  • However, if a change in hormonal therapy is indicated, e.g. due to intolerable adverse effects, the regimen may be modified but change should be minimized thereafter.

• Subjects with metastasis limited to the bone only are excluded. However, subjects with current metastasis limited to the bone only and with a history of distant metastasis are eligible. Subjects with current metastasis limited to the bone only and with current breast tissue lesion are eligible.

• Subjects who have any history of other malignancy (except non-melanoma skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry.

• Subjects with splenectomy.

• Subjects with HIV infection.

• Subjects with any major autoimmune diseases or autoimmune disorders requiring systemic iv/oral steroids or immunosuppressive or immunomodulatory therapies.

  • e.g. Type 1 juvenile onset diabetes mellitus, antibody positive for rheumatoid arthritis, Grave's disease, Hashimoto's thyroiditis, lupus, scleroderma, systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, etc
  • Autoimmune disorders confined to the skin (e.g. psoriasis) are eligible, and topical steroids are allowed for the treatment of such skin disorders.

• Subjects with any known uncontrolled inter-current illness including ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Subjects with any of the following MEDICATIONS within 4 weeks prior to randomization:

  • Anti-neoplastic agents
  • Immunotherapy [mAbs, Interferons, Cytokines (except GCSF)]
  • Immunosuppressants (e.g. Cyclosporin, Rapamycin, Tacrolimus, Rituximab, Alemtuzumab, Natalizumab, etc.).
  • Another investigational drug

• Subjects with pleural effusions and/or ascites, due to malignancy, requiring paracentesis every 2 weeks or more frequently.

• Subjects with any known severe allergies (e.g. anaphylaxis) to any active or inactive ingredients in the study drugs.

• Subjects with bladder inflammation and urinary outflow obstruction.