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Trial record 3 of 8 for:    nut midline carcinoma

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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02698176
First received: February 29, 2016
Last updated: May 23, 2017
Last verified: May 2017
  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.

Condition Intervention Phase
NUT Midline Carcinoma (NMC) Triple Negative Breast Cancer (TNBC) Non-small Cell Lung Cancer (NSCLC) Castration-resistant Prostate Cancer (CRPC) Drug: MK-8628 Dose 1 Drug: MK-8628 Dose 2 Drug: MK-8628 Dose 3 Drug: MK-8628 NMC Cohort Dose Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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) ]

Secondary Outcome Measures:
  • Number of participants with Adverse Events (AEs) [ Time Frame: From time of first dose until the end of follow-up (up to 24 months) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]

Enrollment: 13
Actual Study Start Date: May 4, 2016
Study Completion Date: April 26, 2017
Primary Completion Date: April 26, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8628 Dose Level 1
Participants (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.
Drug: MK-8628 Dose 1
Administered as an oral capsule in a fasted state
Other Name: OTX015
Experimental: MK-8628 Dose Level 2
Participants (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.
Drug: MK-8628 Dose 2
Administered as an oral capsule in a fasted state
Other Name: OTX015
Experimental: MK-8628 Dose Level 3
Participants (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.
Drug: MK-8628 Dose 3
Administered as an oral capsule in a fasted state
Other Name: OTX015
Experimental: NMC Cohort
Participants (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.
Drug: MK-8628 NMC Cohort Dose
Administered as an oral capsule in a fasted state
Other Name: OTX015

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02698176

Locations
United States, Florida
Call for Information (Investigational Site 0023)
Sarasota, Florida, United States, 34232
United States, Massachusetts
Call for Information (Investigational Site 0022)
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Call for Information (Investigational Site 0025)
Philadelphia, Pennsylvania, United States, 19104
Belgium
MSD Belgium BVBA/SPRL
Brussels, Belgium
Canada, Quebec
Merck Canada
Kirkland, Quebec, Canada, H9H 4M7
France
MSD France
Paris, France
Spain
Merck Sharp and Dohme de Espana S.A.
Madrid, Spain
Switzerland
MSD International GmbH
Lucerne 6, Switzerland
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02698176     History of Changes
Other Study ID Numbers: 8628-006
MK-8628-006 ( Other Identifier: Merck Registration Number )
2015-005488-18 ( EudraCT Number )
Study First Received: February 29, 2016
Last Updated: May 23, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
OTX015
MK-8628

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Prostatic Neoplasms
Triple Negative Breast Neoplasms
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 28, 2017