Clinical trial NCT01516307: Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Metastatic Breast Cancer Subjects
Official title: A Double-blind, Randomized Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Subjects With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: OBI Pharma, Inc
Sponsor class: INDUSTRY
First posted: 2012-01-24
Enrollment: 349
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Progression or up to 2 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham (UAB)
state: Alabama
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare, Virginia K. Crosson Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: Orange
country: United States
facility: University of California, Irvine (UCI)
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: San Luis Obispo
country: United States
facility: Coastal Integrative Cancer Care
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Santa Monica
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Asheville
country: United States
facility: Hope Women's Cancer Center
state: North Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Hong-Kong
country: China
facility: UNIMED Medical Institute
city: Bengaluru
country: India
facility: HCG, Bangalore Institute of Oncology
city: Mumbai
country: India
facility: Curie Manavata Cancer Centre
city: Busan-si
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Chungcheongbuk-Do
country: Korea, Republic of
facility: Inha University Hospital
city: Chungcheongbuk-Do
country: Korea, Republic of
facility: National Cancer Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ,
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital-KS
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital -Linkou
city: New Taipei City
country: Taiwan
facility: Mackay Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Medical Center
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital-Taipei
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Shuang-Ho Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
References:
citation: 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.