Clinical trial NCT01463696: Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)
Official title: A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-11-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility 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 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (21 days)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of MK-8242
timeFrame: Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
measure: Time to Maximum Plasma Concentration (Tmax) of MK-8242
timeFrame: Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
measure: Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242
timeFrame: Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12
measure: AUC at Time of Last Sample (AUClast) for MK-8242
timeFrame: Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.