Clinical Trials /

A Dose Exploration Study With MK-8628 in Participants With Selected Advanced Solid Tumors (MK-8628-006)

NCT02698176

Description:

This is a study to determine the recommended dose of MK-8628 (formerly known as OTX015) for further studies in participants with advanced nuclear protein in testis (NUT) midline carcinoma (NMC), triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), or castration-resistant prostate cancer (CRPC). This is a two-part parallel study: Part A will establish the recommended dose by evaluating dose limiting toxicity (DLT), safety, discontinuation, and early efficacy and Part B will enroll participants with NMC only and will evaluate safety and efficacy in this population.

Related Conditions:
  • Breast Carcinoma
  • NUT Midline Carcinoma of the Head and Neck
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose Exploration Study With MK-8628 in Participants With Selected Advanced Solid Tumors (MK-8628-006)
  • Official Title: A Phase IB Dose Exploration Trial With MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Subjects With Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 8628-006
  • SECONDARY ID: MK-8628-006
  • SECONDARY ID: 2015-005488-18
  • NCT ID: NCT02698176

Conditions

  • NUT Midline Carcinoma (NMC)
  • Triple Negative Breast Cancer (TNBC)
  • Non-small Cell Lung Cancer (NSCLC)
  • Castration-resistant Prostate Cancer (CRPC)

Interventions

DrugSynonymsArms
MK-8628 Dose 1OTX015MK-8628 Dose Level 1
MK-8628 Dose 2OTX015MK-8628 Dose Level 2
MK-8628 Dose 3OTX015MK-8628 Dose Level 3
MK-8628 NMC Cohort DoseOTX015NMC Cohort

Purpose

This is a study to determine the recommended dose of MK-8628 (formerly known as OTX015) for further studies in participants with advanced nuclear protein in testis (NUT) midline carcinoma (NMC), triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), or castration-resistant prostate cancer (CRPC). This is a two-part parallel study: Part A will establish the recommended dose by evaluating dose limiting toxicity (DLT), safety, discontinuation, and early efficacy and Part B will enroll participants with NMC only and will evaluate safety and efficacy in this population.

Trial Arms

NameTypeDescriptionInterventions
MK-8628 Dose Level 1ExperimentalParticipants (up to 14) in Part A will receive MK-8628 Dose Level 1. Dose limiting toxicity (DLT) will be used to establish the recommended Phase 2 dose (RP2D) during the first cycle. Participants will continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
  • MK-8628 Dose 1
MK-8628 Dose Level 2ExperimentalParticipants (up to 14) in Part A will receive MK-8628 Dose Level 2. Dose limiting toxicity (DLT) will be used to establish the RP2D during the first cycle. Participants will continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
  • MK-8628 Dose 2
MK-8628 Dose Level 3ExperimentalParticipants (up to 14) in Part A will receive MK-8628 Dose Level 3. Dose limiting toxicity (DLT) will be used to establish the RP2D during the first cycle. Participants will continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
  • MK-8628 Dose 3
NMC CohortExperimentalParticipants (up to 30) in Part B will receive MK-8628 at one dose level below the dose currently being administered in Part A of the study. Once the RP2D from Part A is established, participants in Part B will receive MK-8628 at the RP2D. Participants will continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
  • MK-8628 NMC Cohort Dose

Eligibility Criteria

        Inclusion Criteria:

          -  Males and females ≥18 years of age for NSCLC, TNBC, and CRPC

          -  Males and females ≥16 years of age for NMC

          -  Diagnosis of one of the following advanced solid tumors for which standard therapy
             either does not exist or has proven ineffective, intolerable or inacceptable for the
             participant: NMC;TNBC; NSCLC; or CRPC

          -  Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1. CRPC participants may be enrolled with objective evidence of disease as
             per Prostate Cancer Working Group (PCWG2) criteria

          -  Life expectancy ≥3 months

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

          -  Have an interval of ≥3 weeks (or ≥2 weeks for NMC participants) since chemotherapy (≥6
             weeks for nitrosoureas or mitomycin C), immunotherapy, hormone therapy or any other
             anticancer therapy or surgical intervention resection, or ≥3 half-lives for monoclonal
             antibodies, or ≥5 half-lives for other non-cytotoxic agents (whichever is longer)

          -  CRPC participants must maintain ongoing androgen deprivation therapy with a
             gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing
             serum testosterone is <50 ng/dL (<1.7 nmol/L)

          -  Participants receiving bisphosphonate or denosumab therapy must be on stable doses for
             at least 4 weeks before start of study therapy

          -  Females must not be pregnant (negative urine or serum human chorionic gonadotropin
             test within 72 hours of study start)

          -  Females of childbearing potential and male participants must agree to use adequate
             contraception starting with the first dose of trial treatment through 90 days after
             the last dose of study medication

        Exclusion Criteria:

          -  Has inability to swallow oral medications or presence of a gastrointestinal disorder
             (e.g. malabsorption) deemed to jeopardize intestinal absorption of MK-8628

          -  Has persistent grade >1 clinically significant toxicities related to prior
             antineoplastic therapies (except for alopecia). Stable sensory neuropathy ≤ grade 2
             National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events
             (CTCAE) Version 4.0 is accepted

          -  Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS
             metastases. Treated and stable CNS metastases are allowed.

          -  History of prior or concomitant malignancies within 3 years of study start

          -  Have other serious illness or medical condition, such as active infection, unresolved
             bowel obstruction, psychiatric disorders, or cerebrovascular accident within 1 year of
             study start

          -  Known human immunodeficiency virus (HIV) and/or active Hepatitis B or C infections

          -  Have one of the following cardiac-related conditions: Congestive heart failure or
             angina pectoris (except if medically controlled); myocardial infarction (within 1 year
             of study start); uncontrolled hypertension; or uncontrolled arrhythmias

          -  Other concomitant anticancer treatment

          -  Participation in another clinical trial or treatment with any investigational drug
             (excluding anticancer treatments) within 30 days of study start

          -  Concomitant therapy with strong CYP3A4 inhibitors or inducers

          -  Therapeutic anticoagulation (e.g. warfarin, heparin, etc.) must be stopped at least 7
             days prior to the first dose of MK-8628. Low-dose low molecular weight heparin (LMWH)
             is permitted

          -  Is pregnant or breast-feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants with a Dose Limiting Toxicity (DLT)
Time Frame:From time of first dose up to the end of the first cycle (up to 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants with Adverse Events (AEs)
Time Frame:From time of first dose until the end of follow-up (up to 24 months)
Safety Issue:
Description:
Measure:Number of participants discontinuing study drug due to AEs
Time Frame:From time of first dose until the end of follow-up (up to 24 months)
Safety Issue:
Description:
Measure:Percentage of Participants who Achieve Complete Tumor Response or Partial Tumor Response (ORR) determined using the best overall response
Time Frame:Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Safety Issue:
Description:
Measure:Time from Complete or Partial Tumor Response to Documented Disease Progression or Death (DOR)
Time Frame:Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Safety Issue:
Description:
Measure:Percentage of Participants who Achieve Stable Disease or Complete or Partial Tumor Response (DCR)
Time Frame:Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • OTX015
  • MK-8628

Last Updated

May 23, 2017