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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Biological: OPT-822/OPT-821(30 μg/100 μg); Drug: Cyclophosphamide; Biological: Phosphate Buffer Saline (PBS)

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong-Kong, China
    • UNIMED Medical Institute
• India
  • Bengaluru, India
    • HCG, Bangalore Institute of Oncology
  • Mumbai, India
    • Curie Manavata Cancer Centre
• Korea, Republic of
  • Busan, Korea, Republic of
    • Dong-A University Hospital
  • Busan-si, Korea, Republic of
    • Pusan National University Hospital
  • Chungcheongbuk-Do, Korea, Republic of
    • Inha University Hospital
  • Chungcheongbuk-Do, Korea, Republic of
    • National Cancer Center
  • Daegu, Korea, Republic of
    • Yeungnam University Medical Center
  • Daegu, Korea, Republic of
    • Kyungpook National University Medical Center
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital ,
• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan
    • Chang Gung Memorial Hospital-KS
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Hospital
  • Kaohsiung City, Taiwan
    • Kaohsiung Veterans General Hospital
  • Linkou, Taiwan
    • Chang Gung Memorial Hospital -Linkou
  • New Taipei City, Taiwan
    • Mackay Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Tainan City, Taiwan
    • Chi Mei Medical Center
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Chang Gung Memorial Hospital-Taipei
  • Taipei, Taiwan
    • Shuang-Ho Hospital
  • Taipei City, Taiwan
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan
    • Koo Foundation Sun Yat-Sen Cancer Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham (UAB)
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Healthcare, Virginia K. Crosson Cancer Center
    • La Jolla, California, United States, 92093
      • University of California, San Diego (UCSD)
    • Orange, California, United States, 92868
      • University of California, Irvine (UCI)
    • San Francisco, California, United States, 94115
      • University of California, San Francisco (UCSF)
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
    • Santa Monica, California, United States, 90404
      • University of California, Los Angeles (UCLA)
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Hope Women's Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	5 years

Collaborators and Investigators

• Sponsor: OBI Pharma, Inc

Publications and helpful links

General Publications

• Huang CS, Yu AL, Tseng LM, Chow LWC, Hou MF, Hurvitz SA, Schwab RB, L Murray J, Chang HK, Chang HT, Chen SC, Kim SB, Hung JT, Ueng SH, Lee SH, Chen CC, Rugo HS. Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. J Immunother Cancer. 2020 Jul;8(2):e000342. doi: 10.1136/jitc-2019-000342.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: OPT-822-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No