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

NCT01463696 | Terminated Phase 1 Results

• 3 other identifiers: P076502011-001346-15MK-8242-006
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was defined as: any drug-related hematologic toxicity ≥ Grade 3 lasting ≥1 week, ≥ Grade 3 thrombocytopenia with bleeding, ≥ Grade 3 neutropenia with infection OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions/clarifications: 1) Grade 3 nausea, vomiting, diarrhea, and dehydration were excluded from the determination of DLT if, in the opinion of the investigator and sponsor, they occurred in a setting of inadequate treatment, 2) Grade 3 nausea, vomiting, diarrhea, and dehydration were each considered a DLT if they persisted despite 72 hours of maximal supportive care measures or 3) Any abnormal non-hematological laboratory value ≥ Grade 3 (that is not attributable to any other causes) was considered a DLT only if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for ≥1 week.

  Cycle 1 (21 days)

Secondary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of MK-8242

  Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

• Time to Maximum Plasma Concentration (Tmax) of MK-8242

  Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

• Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242

  Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12

• AUC at Time of Last Sample (AUClast) for MK-8242

  Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

Study Arms (8)

MK-8242 60 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 60 mg administered orally (PO) twice a day (BID) on Days 1-6 and PO once daily (QD) in the morning on Day 7 of the 21-day cycle to accommodate pharmacokinetic (PK) sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 60 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 120 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 120 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 120 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 170 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 170 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 170 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 250 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 250 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 250 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 300 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 300 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 300 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 350 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 350 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 350 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 400 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 400 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 400 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

MK-8242 500 mg BID

EXPERIMENTAL

In Cycle 1, participants received MK-8242 500 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 500 mg PO BID on Days 1-7 of each 21-day cycle.

Drug: MK-8242

Interventions

MK-8242 DRUG

10 mg, 100 mg and 150 mg capsules

Also known as: SCH 900242

MK-8242 120 mg BID; MK-8242 170 mg BID; MK-8242 250 mg BID; MK-8242 300 mg BID; MK-8242 350 mg BID; MK-8242 400 mg BID; MK-8242 500 mg BID; MK-8242 60 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 drug
• At least one measurable lesion
• In Part 2, participants with liposarcoma must have a confirmed well-differentiated or de-differentiated histology

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Wagner AJ, Banerji U, Mahipal A, Somaiah N, Hirsch H, Fancourt C, Johnson-Levonas AO, Lam R, Meister AK, Russo G, Knox CD, Rose S, Hong DS. Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors. J Clin Oncol. 2017 Apr 20;35(12):1304-1311. doi: 10.1200/JCO.2016.70.7117. Epub 2017 Feb 27.

  PMID: 28240971 RESULT

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 2, 2011
• Study Start: December 21, 2011
• Primary Completion: September 15, 2014
• Study Completion: October 15, 2015
• Last Updated: August 27, 2018
• Results First Posted: May 23, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share