Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01463696
First received: October 28, 2011
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

This study is being done to evaluate the safety and pharmacokinetic profile of MK-8242 and its active metabolite (M16) in participants with advanced solid tumors. In Part 1 of the study, the study drug dose will be escalated to determine the maximum tolerated dose (MTD). In Part 2 of the study, the MTD will be confirmed and the recommended Phase 2 dose (RPTD) established; the effect of MK-8242 on liposarcoma and other tumor types will also be evaluated.


Condition Intervention Phase
Solid Tumors
Drug: MK-8242
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (21 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) of MK-8242 [ Time Frame: Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose ] [ Designated as safety issue: No ]
  • Time to maximum plasma concentration (Tmax) of MK-8242 [ Time Frame: Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose ] [ Designated as safety issue: No ]
  • Area under the concentration time curve from Hour 0 to Hour 12 (AUC0-12) for MK-8242 [ Time Frame: Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12 ] [ Designated as safety issue: No ]
  • AUC from time 0 to the time of final quantifiable sample (AUCtf) for MK-8242 [ Time Frame: Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 86
Study Start Date: December 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: MK-8242 dose escalation Drug: MK-8242
MK-8242 capsules will be administered orally twice a day (BID) on Days 1-6 of Cycle 1 and once in the morning (QD) on Day 7 of a 21-day cycle to accommodate pharmacokinetic (PK) sampling. In Cycle 2 and subsequent cycles, MK-8242 will be administered orally twice a day (BID) on Days 1-7 in a 21-day cycle.
Other Name: SCH 900242
Experimental: Part 2: MK-8242 dose confirmation Drug: MK-8242
MK-8242 capsules will be administered orally twice a day (BID) on Days 1-6 of Cycle 1 and once in the morning (QD) on Day 7 of a 21-day cycle to accommodate pharmacokinetic (PK) sampling. In Cycle 2 and subsequent cycles, MK-8242 will be administered orally twice a day (BID) on Days 1-7 in a 21-day cycle.
Other Name: SCH 900242

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Histologically confirmed advanced solid tumor for which there are no effective standard therapy options
  • Willing to provide tumor tissue for p53 wild type gene analysis Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
  • Adequate organ function
  • Female participants and male participants and their partners who are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study therapy
  • At least one measurable lesion
  • In Part 2, participants with liposarcoma must have a confirmed well-differentiated or de-differentiated histology

Exclusion criteria:

  • Known treated or untreated leptomeningeal metastases, or metastatic central nervous system disease
  • History of recent myocardial infarction (within the past year); or with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality
  • Uncontrolled active infection on optimal systemic treatment
  • Clinically significant hepatitis or hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive
  • Persistent, unresolved common terminology criteria for adverse events (CTCAE v4.0) ≥Grade 2 drug-related toxicity associated with previous treatment except for alopecia
  • Radiation therapy or other loco-regional therapy within 2 weeks prior to study
  • Use of moderate and strong Cytochrome P450 inhibitors or inducers within 1 week prior to study
  • Chemotherapy or any investigational drug(s) within 4 weeks prior to study
  • Known hypersensitivity to MK-8242 or its components
  • Nursing, pregnant, or intention to become pregnant during the study
  • Initiating bisphosphonate therapy or adjusting the bisphosphonate dose or regimen within 30 days of Cycle 1 Day 1
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01463696     History of Changes
Other Study ID Numbers: P07650, 2011-001346-15
Study First Received: October 28, 2011
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014