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

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Biological: OPT-822/OPT-821(30 μg/100 μg)
* Biological: Phosphate Buffer Saline (PBS)
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPT-822/OPT-821 (30 μg/100 μg) and Cyclophosphamide<br>Patients will be randomized 2:1 to receive OPT-822/OPT-821(30 μg/100 μg) plus Cyclophosphamide IV (300mg/m2). | Biological: OPT-822/OPT-821(30 μg/100 μg)<br>* Subcutaneously on week 1, 2, 3, 5, 9, 13, 17, 25, and 37. OPT-822 and OPT-821 are combined at time of injection.<br>Drug: Cyclophosphamide<br>* Subcutaneously on week 1, 2, 3, 5, 9, 13, 17, 25, and 37.<br>|
| Placebo Comparator: Phosphate Buffer Saline (PBS) and Cyclophosphamide<br>Patients will receive Phosphate Buffer Saline (PBS) plus Cyclophosphamide IV (300mg/m2). | Biological: Phosphate Buffer Saline (PBS)<br>* Subcutaneously on week 1, 2, 3, 5, 9, 13, 17, 25, and 37.<br>Drug: Cyclophosphamide<br>* Subcutaneously on week 1, 2, 3, 5, 9, 13, 17, 25, and 37.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Progression or up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | 5 years |