To Evaluate OBI-833/OBI-821 in Patients With Locally Advanced, Globo H-Positive Esophageal Cancer for Recurrence
Study Details
Study Description
Brief Summary
A Phase 2 Study to Evaluate Adjuvant OBI-833/OBI-821 Therapy in Patients With Locally Advanced, Globo H-Positive Esophageal Cancer at High Risk for Recurrence
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OBI-833/OBI-821 OBI-833 consists of Globo H, a unique tumor-associated carbohydrate antigen (TACA), covalently linked to cross-reacting material 197 (CRM197), an inactive and nontoxic form of diphtheria toxin (DT) acting as a carrier protein. OBI-821 is a purified saponin adjuvant Dosage form: solution Dosage:30 μg OBI-833/100 μg OBI-821, subcutaneous injection, Frequency: weekly for 4 doses (weeks 1, 2, 3, 4), then every 2 weeks for 2 doses (weeks 6, 8), then every 4 weeks for 4 doses (weeks 12, 16, 20, 24), and then every 8 weeks until disease recurrence, intolerable adverse events/toxicity, consent withdrawal, death, or up to 80 weeks from randomization. |
Biological: OBI-833/OBI-821
OBI-833 and OBI-821 are individually formulated into separate glass vials. The articles are mixed prior to subcutaneous administration at the clinic.
|
| No Intervention: Observation Patients will be randomized into OBI-833/OBI-821 (experimental) arm or observation arm. |
Outcome Measures
Primary Outcome Measures
- Recurrence-free survival rate [one year]
To evaluate the effect of OBI-833/OBI-821 treatment on improving recurrence-free survival in patients with locally advanced, Globo H-positive esophageal cancer in the adjuvant setting
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female patients, 20 years of age or older at the time of consent.
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Pathologically or cytologically confirmed diagnosis of esophageal cancer (including squamous cell carcinoma and adenocarcinoma) whose postneoadjuvant pathologic stage is ypT1-4 AND ypN1-3 according to the AJCC Cancer Staging System, 8th Edition.
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Patients have been treated with preoperative cisplatin-based chemoradiotherapy followed by esophagectomy with lymph node dissection for locally advanced esophageal cancer (defined by the above criterion).
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Postneoadjuvant pathologic staging: ypT1-4 and ypN1-3.
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Globo H IHC H-score ≥1 in the surgical tumor specimen from the primary site/or lymph node (if the primary site is not available). The Globo H expression will be determined by a qualified laboratory.
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R0 (no residual tumor on the surgical margin of the resected tumor specimen).
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Organ Function Requirements - Subjects must have adequate organ functions as defined below:
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AST/ALT ≤ 3X ULN (upper limit of normal)
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Total bilirubin ≤ 2X ULN
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Serum creatinine ≤ 1.5X ULN
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ANC ≧ 1,500 /μL
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Platelets ≧ 100,000/μL
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All eligible patients of childbearing potential must use effective contraception during study treatment and for at least 2 months after the last dose of OBI-833/OBI-821. Subjects not of childbearing potential (i.e., permanently sterilized, postmenopausal) can be included in the study. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
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Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria:
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Subjects who cannot be randomized within 8 weeks after the esophageal cancer surgery.
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Subjects who are pregnant or breast-feeding at entry.
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Subjects with splenectomy.
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Has prior malignancy, except (a) adequately treated basal cell or squamous cell skin cancer; (b) in situ cervical cancer; (c) previously diagnosed malignancy which has been adequately treated and shown no evidence of recurrence for more than 5 years.
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Subjects with HIV infection, active hepatitis B infection, or active hepatitis C infection.
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Subjects with any autoimmune or other disorders requiring IV/oral steroids or immunosuppressive or immunomodulatory therapies.
- e.g., type 1 juvenile-onset diabetes mellitus, antibody positive for rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, lupus, scleroderma, systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, Crohn disease, ulcerative colitis, and psoriasis.
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Subjects with any known uncontrolled comorbid illness, including ongoing or active infections, symptomatic congestive heart failure (NYHA>2), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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Subjects who have received any of the following medications within 4 weeks prior to randomization:
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Immunotherapy, including monoclonal antibodies, cytokines, interferons, and checkpoint inhibitors.
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Immunosuppressants, including cyclosporin, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab, and cyclophosphamide.
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Other biologics, including G-CSF and other hematopoietic growth factors.
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Live attenuated vaccines.
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IV/oral steroids except single prophylactic use in CT/MRI scan or other one-time use in approved indications. Use of inhaled and topical (except on the injection site) steroids is allowed.
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Alternative and complementary medicine that may affect the immune system.
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Other investigational drugs
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Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Grade 0 or 1 (using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), except for alopecia and laboratory values listed in the inclusion criteria.
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Subjects with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in the study drugs.
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Any other reason that the investigator deems the patient as unsuitable for the study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- National Taiwan University Hospital
Investigators
- Principal Investigator: Jang-Ming Lee, Department of Surgery, National Taiwan University Hospital. Taipei, Taiwan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 202106018MIPB