Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001)

Merck Sharp & Dohme LLC35 enrolled

Overview

This study will investigate the safety, side effects and how well the body tolerates MK-5108 as well as determine different doses of MK-5108 in participants with advanced and/or refractory solid tumors. The corresponding primary hypotheses of this study are that 1) administration of oral MK-5108 (twice daily for 2 out of 14-21 days) to participants with advanced and/or refractory solid tumors will be safe and tolerable, and that 2) the spectrum of side effects observed in these participants after administration of oral MK-5108 alone and in combination with docetaxel will be dose-dependent and allow for definition of a maximum tolerated dose (MTD).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cancer, Neoplasms, Tumors

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Participant has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy or progressed with standard therapy Exclusion Criteria: * Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks prior to study start or has not recovered from adverse events caused by therapy more than 4 weeks earlier * Participant is currently participating or has participated in a study with an investigational compound or device within 4 weeks prior to signing informed consent * Participant has received more than 2 courses of chemotherapy for metastatic disease * Participant has had prolonged neutropenia or neutropenia with fever from previous chemotherapy treatment * Participant has a primary central nervous system tumor * Participant is a regular or recreational user of any illicit drugs or has a recent history within the last year of drug or alcohol abuse * Participant is pregnant, breastfeeding or planning to have children during the study * Participant is Human Immunodeficiency Virus (HIV) positive * Participant has a history of Hepatitis B or C

Outcomes

Primary Outcomes

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants who experienced an AE was reported for each dose level group.

Time frame: From Day 1 of study treatment until 30 days following the last dose of study treatment (up to 577 days)

Number of Participants With Dose Limiting Toxicities (DLTs)

DLTs were AEs considered related to study drug that prevented escalation of the drug dose. Hematologic DLTs included any Grade 5 hematologic toxicity, Grade 4 neutropenia lasting for ≥7 days in duration, Grade 3 or Grade 4 neutropenia with fever \>38.5°C and/or infection requiring antibiotic or anti-fungal treatment, and Grade 4 thrombocytopenia (≤25.0 x 10\^9/L). Non-hematologic DLT was defined as any Grade 3, 4, or 5 non-hematologic toxicity, with the specific exceptions of: Grade 3 nausea or Grade 3 vomiting, Grade 3 diarrhea, or Grade 3 dehydration occurring in the setting of inadequate compliance with supportive care and lasting for \<48 hours, alopecia, inadequately treated hypersensitivity reactions, or Grade 3 elevated transaminases of ≤1 week in duration. Any drug-related AE leading to a dose modification of MK-5108, or any unresolved drug-related toxicity persisting\>6 weeks, was also considered a DLT.

Time frame: Day 1 to Day 21 of study treatment (Cycle 1 for Panel 1, Panel 2, or Crossover)