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Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy.

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ClinicalTrials.gov Identifier: NCT03562637
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
OBI Pharma, Inc

Brief Summary:
This is a Phase III, randomized, double-blind, placebo controlled, study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 treatment, compared to placebo, in patients with early stage TNBC at high risk for recurrence.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Biological: adagloxad simolenin combined with OBI-821 Biological: Phosphate-buffered saline (PBS) Device: Globo H IHC Assay Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 668 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-blind, Placebo Controlled Study of Adagloxad Simolenin (OBI 822)/OBI 821 Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients, Defined as Residual Invasive Disease Following Neoadjuvant Chemotherapy OR ≥4 Positive Axillary Nodes
Actual Study Start Date : December 5, 2018
Estimated Primary Completion Date : November 30, 2025
Estimated Study Completion Date : November 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Adagloxad simolenin + OBI-821
Participants will be administered adagloxad simolenin combined with OBI-821 for up to a total of 21 subcutaneous injections at week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100.
Biological: adagloxad simolenin combined with OBI-821
In the neoadjuvant and adjuvant phases of the study for a total 100 weeks; subcutaneously injections.

Device: Globo H IHC Assay
The Globo H IHC assay will be used to identify eligible patients who may clinically benefit from the OBI-822 treatment, defined by Globo H expression.

Active Comparator: Placebo
Participants will be administered placebo for up to a total of 21 subcutaneous injections at week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100.
Biological: Phosphate-buffered saline (PBS)
In the neoadjuvant and adjuvant phases of the study for a total 100 weeks; subcutaneously injections.

Device: Globo H IHC Assay
The Globo H IHC assay will be used to identify eligible patients who may clinically benefit from the OBI-822 treatment, defined by Globo H expression.




Primary Outcome Measures :
  1. Measuring the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease free survival (IDFS) in the study population. [ Time Frame: 5 years ]
    IDFS is defined as the time interval from the "date of randomization to the date of objective invasive tumor recurrence" i.e., the appearance of any new invasive lesion(s), during or after study treatment.


Secondary Outcome Measures :
  1. Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in TNBC patients at high risk for relapse on Overall Survival (OS). [ Time Frame: 7 years ]
    OS is defined as the time from randomization to date of death from any cause

  2. Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in TNBC patients at high risk for relapse, on Quality of Life (QoL). [ Time Frame: 7 years ]

    QoL defined as time to definitive deterioration in Health-related Quality of Life (HRQOL) using the global health status/QoL scale from European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). QoL baseline established at randomization. Definitive deterioration defined as a 5% worsening relative to baseline in the HRQOL scale score from EORTC QLQ-C30 questionnaires with no subsequent improvement above this threshold.

    28 questions have a four-point scale, ranging from "not at all" (1) to "very much" (4). 2 questions have a 7-point scale, ranging from "very poor" (1) to "excellent" (7). The results are scored with the EORTC QLQ-C30 v3.0 Scoring Manual. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/QoL represents a good QoL. A high score for symptom and single-item scales represent a high level of symptomatology.


  3. Incidence and severity of adverse events (AEs) [Time Frame: AEs will be noted as it occurs, with a timeframe from beginning of randomization to 4 weeks after last dose of study treatment.] [ Time Frame: 2 years ]
    Adverse Events will be graded and recorded by investigators per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).

  4. Incidence of a change from baseline in safety parameters related to 12-lead electrocardiogram (ECG) [Time Frame: ECGs will be conducted from time of screening to end of treatment.] [ Time Frame: 2 years ]
    Resting 12-lead ECGs will be obtained at time of screening, week 12, and thereafter every 24-28 weeks duration until end of study. A final ECG will be performed at end of treatment. In addition, unscheduled ECGs may be conducted under investigator's discretion in the event of significant cardiovascular-related medical event or when clinically indicated.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented radiographic and histopathologic confirmed primary localized invasive breast cancer.
  • Histologically documented TNBC (ER-/PR-/HER2-) defined as ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and negative HER2/neu- status, confirmed on tumor biopsy sample from surgery.
  • HER2/neu negative will be defined as one of the following criteria:

    • IHC 0 or 1+
    • Single-probe average HER2 gene copy number of <6 signals/nucleus
    • Dual-probe FISH HER2/neu chromosome 17 (CEP17) non-amplified ratio of <2
  • Globo H IHC H-score ≥15 in the tumor tissue biopsy from the primary site/or lymph node (if primary site is not available). The Globo H expression will be determined during Pre-screening Phase by Central lab. Instructions for submission of slides/tumor tissues block and pertinent reports to central review are provided in the study Lab Manual.
  • No evidence of metastatic disease in chest, abdomen and pelvis by CT or MRI scan during the Screening Phase. Historical report within 3 months prior to randomization is acceptable as baseline scan. Bone scans and imaging of the brain at screening is optional, and should be symptom directed.
  • High risk patients meeting ONE of the following criteria:

    • Neoadjuvant chemotherapy: Residual invasive disease following neoadjuvant chemotherapy defined as: A contiguous focus of residual invasive cancer in the breast measuring ≥1 cm in diameter with more than 1% cellularity and/or with residual invasive cancer in at least one axillary node (as determined by local pathology review)
    • Primary surgery: Patients must have ≥4 axillary lymph nodes positive for invasive cancer and have completed adjuvant chemotherapy
  • Must have completed taxane (with or without platinum), and/or anthracycline-based chemotherapy (either sequential or concurrent) either in the neoadjuvant or adjuvant setting.

    • Post-neoadjuvant chemotherapy with capecitabine or a platinum salt is allowed.

  • Surgery for treatment of primary cancer must be completed at least 2 weeks, but no more than 56 weeks, prior to randomization. Patients receiving neoadjuvant therapy who are not receiving post-operative (adjuvant) chemotherapy must have completed their final breast surgery no more than 32 weeks prior to randomization.
  • All adjuvant chemotherapy and/or radiotherapy (if indicated) after surgery, must have been completed at least 2 weeks prior to randomization.
  • All treatment-related toxicities resolved to Grade <1 on National cancer institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria (except hair loss and ≤Grade 2 neuropathy, which are acceptable).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Females must be either of non-childbearing potential, i.e., surgically sterilized (have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months before the start of the trial and/or hysterectomy), or one year postmenopausal; or if of childbearing potential must have a negative pregnancy test (urine or serum) at randomization.
  • Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire study treatment period and for at least 4 weeks after the last dose of study treatment.
  • Adequate hematological, hepatic and renal function as defined below:

    • Absolute neutrophil count (ANC) ≥1,500/µL
    • Platelets ≥75,000/µL
    • Hemoglobin ≥8.5g/dL
    • Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥55 mL/min for subjects with creatinine levels >1.5 × institutional ULN (glomerular filtration rate can also be used in place of creatinine or creatinine clearance may be calculated per institutional standard)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
    • Alkaline Phosphatase (ALP) ≤2.5 × ULN
    • Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented)
  • Left ventricular ejection fraction (LVEF) ≥ the institutional lower limit of normal, by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  • Consent to participate with a signed and dated IRB-approved patient informed consent for the study prior to beginning any specific study procedures.
  • Ability to understand and willingness to complete all protocol required procedures.

Exclusion Criteria:

  • Local recurrence of or previous history of contralateral invasive breast cancer within 10 years of the current diagnosis.
  • Definitive clinical or radiologic evidence of metastatic disease
  • Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.
  • Have received immunotherapy with antigen, antibody, immune checkpoint inhibitors (Programmed cell death-1/ Programmed cell death-ligand-1inhibitors, anti-cytotoxic T lymphocyte associated protein 4 [CTLA 4] therapy), or other anti-cancer vaccines within 4 weeks prior to randomization.
  • For patients undergoing neoadjuvant chemotherapy, more than one line of chemotherapy following surgery.
  • A history of other malignancies (except non melanoma skin carcinoma, carcinoma in situ of the uterine cervix, non-invasive follicular thyroid neoplasm and papillary thyroid cancer) within 5 years prior to this breast cancer diagnosis.
  • Have any active autoimmune disease or disorder that requires systemic immunosuppressive/immunomodulatory therapy. NOTE: Autoimmune diseases that are confined to the skin (e.g., psoriasis) that can be treated with topical steroids alone are allowed during the study.
  • Oral/parenteral corticosteroid treatment (>5 mg/day of prednisone/equivalent), within 2 weeks prior to randomization or anytime during the study. NOTE: inhaled steroids for treatment of asthma; and topical steroids are allowed during the study.
  • Any known uncontrolled concurrent illness that would limit compliance with study requirements, including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric disorders, or substance abuse.
  • Any known hypersensitivity to active/inactive ingredients in the study drug formulation or known severe allergy or anaphylaxis to fusion proteins.
  • Receipt of any live, attenuated vaccine (including influenza vaccine, e.g., FluMist) within 4 weeks prior to randomization and during the study till 4 weeks after the last dose of study treatment. NOTE: inactivated vaccines (e.g., inactivated influenza vaccines) are allowed during the study, if required.
  • Prior receipt of a glycoconjugate vaccine for cancer immunotherapy; or has received glycoconjugate vaccine for bacterial infections within 4 weeks prior to randomization.
  • Known history or positive for human immunodeficiency virus (HIV positive)
  • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Active infections are HBVsAg positive, HBV DNA ≥1000 cps/mL or 200 IU/mL or positive HCV RNA test.
  • Any condition, including significant diseases and/or laboratory abnormalities that would place the subject at unacceptable risk for study participation.
  • Currently pregnant or breastfeeding women.
  • Currently participating in a clinical study, and receiving an investigational drug or has participated in a therapeutic clinical trial within 4 weeks prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03562637


Contacts
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Contact: Lisa Liang +866 2-2786-6589 lliang@obipharma.com
Contact: Michelle Tien mtien@obipharma.com

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Sponsors and Collaborators
OBI Pharma, Inc
Investigators
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Study Chair: Hope Rugo, MD University of California, San Francisco

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Responsible Party: OBI Pharma, Inc
ClinicalTrials.gov Identifier: NCT03562637     History of Changes
Other Study ID Numbers: OBI-822-011
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by OBI Pharma, Inc:
Neoadjuvant chemotherapy
Adjuvant chemotherapy
TNBC
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases