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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Solid Tumors

Treatments: Drug: MK-8242

Study type: Interventional

Funder types: Industry

Identifiers

NCT01463696

2011-001346-15 (EudraCT Number)

P07650

MK-8242-006 (Other Identifier)

Details and patient eligibility

About

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.

Full description

Participants are considered to have completed the study after Cycle 12. Amendment 4 (14 April 2015) was done to allow participants on active treatment at the time the study was closed to enrollment to continue study treatment beyond Cycle 12 if deriving clinical benefit, at the Investigator's discretion.

Enrollment: 48 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 drug
• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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48 participants in 8 patient groups

MK-8242 60 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 120 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 170 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 250 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 300 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 350 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 400 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242

MK-8242 500 mg BID

Experimental group

Description:

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.

Treatment:

Drug: MK-8242