Clinical Trials /

Study of BMS-986158 in Subjects With Select Advanced Cancers

NCT02419417

Description:

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-986158 in subjects with select advanced cancers

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">BMS-986158</span> in Subjects With Select Advanced Solid Tumors

Title

  • Brief Title: Study of BMS-986158 in Subjects With Select Advanced Solid Tumors
  • Official Title: A Phase I/IIa Trial With BMS-986158, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Subjects With Selected Advanced Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02419417

    ORG ID: CA011-001

    NCI ID: 2015-000324-29

    Trial Conditions

    Multiple Indications Cancer

    Trial Interventions

    Drug Synonyms Arms
    BMS-986158 Part 1 A (Dose Escalation): Treatment Arm A, Part 1A (Dose Escalation): Treatment Arm B, Part 1A (Dose Escalation): Treatment Arm C, Part 2A (Dose Expansion): Treatment Arm A, Part 2A (Dose Expansion): Treatment Arm B, Part 2A (Dose Expansion): Treatment Arm C

    Trial Purpose

    The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and
    pharmacodynamics of BMS-986158 in subjects with select advanced solid tumors.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Part 1 A (Dose Escalation): Treatment Arm A Experimental Subjects will be treated at increasing doses of BMS-986158 until the maximum tolerated dose is reached. BMS-986158
    Part 1A (Dose Escalation): Treatment Arm B Experimental Subjects will be treated at increasing doses of BMS-986158 until the maximum tolerated dose is reached. BMS-986158
    Part 1A (Dose Escalation): Treatment Arm C Experimental Subjects will be treated at increasing doses of BMS-986158 until the maximum tolerated dose is reached. BMS-986158
    Part 2A (Dose Expansion): Treatment Arm A Experimental Subjects will be treated at maximum tolerated dose. BMS-986158
    Part 2A (Dose Expansion): Treatment Arm B Experimental Subjects will be treated at maximum tolerated dose. BMS-986158
    Part 2A (Dose Expansion): Treatment Arm C Experimental Subjects will be treated at maximum tolerated dose. BMS-986158

    Eligibility Criteria

    For more information regarding BMS clinical trial participation, please visit
    www.BMSStudyConnect.com

    Inclusion Criteria:

    - Must have triple negative breast cancer, ovarian (Serous histology for expansion
    phase), small cell lung cancer, or other solid tumors

    - Expected to have life expectancy of at least 3 months

    - Men and women 18 years old or older

    - At least one measurable lesion at baseline by CT or MRI as per response evaluation
    criteria in solid tumors (RECIST) v1.1

    - Eastern Cooperative Oncology Group (ECOG) of 0 to 1

    Exclusion Criteria:

    - Serious or uncontrolled medical disorders

    - Concomitant second malignancies

    - Uncontrolled or significant cardiovascular disease

    - Inadequate bone marrow function

    Other protocol defined inclusion/exclusion criteria could apply

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety as measured by the rate of adverse events (AEs) and Serious Adverse Events (SAEs)

    Secondary Outcome Measures

    Best Overall Response

    Objective Response Rate (ORR)

    Duration of Response

    Progression Free Survival (PFS)

    Progression Free Survival Rate (PFSR) at week 't'

    Maximum observed plasma concentration (Cmax) for single dose of BMS-986158

    Time of maximum observed plasma concentration (Tmax) for single dose of BMS-986158

    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) for single dose of BMS-986158

    Area under the concentration-time curve in one dosing interval (AUC(TAU)) for single dose of BMS-986158

    Apparent terminal phase half-life (T-HALF) for single dose of BMS-986158

    Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for single dose of BMS-986158

    Apparent total body clearance, reported only for parent, not for metabolite (CLT/F) for single dose of BMS-986158

    Apparent volume of distribution of terminal phase, reported only for parent, not for metabolite (Vz/F) for single dose of BMS-986158

    Maximum observed plasma concentration (Cmax) for multiple dose of BMS-986158

    Time of maximum observed plasma concentration (Tmax) for multiple dose of BMS-986158

    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) for multiple dose of BMS-986158

    Area under the concentration-time curve in one dosing interval (AUC(TAU)) for multiple dose of BMS-986158

    The minimum observed concentration within a dosing interval (Cmin) for multiple dose of BMS-986158

    Concentration at the end of a dosing interval (Ctau) for multiple dose of BMS-986158

    Trough observed plasma concentration (this includes predose concentrations (C0) and concentrations at the end of dosing interval (Ctau)) (Ctrough) for multiple dose of BMS-986158

    Degree of Fluctuation or Fluctuation Index ([Cmax-Cmin)/Css-avg]) (DF) for multiple dose of BMS-986158

    [Cmax - Cmin] / Cmin; to be calculated at steady-state (Swing) for multiple dose of BMS-986158

    Accumulation Index (AI) for multiple dose of BMS-986158

    Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (T-HALFeff) for multiple dose of BMS-986158

    Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax)

    Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight (MR_AUC(0-T))

    Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight (following single dose only) (MR_AUC(INF))

    Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight (MR_AUC(TAU))

    Summary Changes in Expression of BET regulated Genes in Blood

    Changes in QTcF

    Trial Keywords