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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.

NCT03562637

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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.
  • 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

Clinical Trial IDs

  • ORG STUDY ID: OBI-822-011
  • NCT ID: NCT03562637

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
adagloxad simolenin combined with OBI-821Adagloxad simolenin + OBI-821
Phosphate-buffered saline (PBS)Placebo

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Adagloxad simolenin + OBI-821ExperimentalParticipants 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.
    PlaceboActive ComparatorParticipants 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.

      Eligibility 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 (Section 9.4.9) and
                   for at least 8 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 any systemic treatment for TNBC within 2 weeks prior to randomization.
      
                -  Have received neo/adjuvant anti-cancer treatment or 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.
      
                -  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.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure: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
      Safety Issue:
      Description: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

      Measure: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
      Safety Issue:
      Description:OS is defined as the time from randomization to date of death from any cause
      Measure: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
      Safety Issue:
      Description: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.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:OBI Pharma, Inc

      Trial Keywords

      • Neoadjuvant chemotherapy
      • Adjuvant chemotherapy
      • TNBC

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