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

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
A Phase I Investigation of MK-5108 and MK-5108 With Docetaxel in Patients With Advanced Solid Tumors

Conditions
-----------------
Cancer, Neoplasms, Tumors

Intervention / Treatment
-----------------
* Drug: MK-5108
* Drug: docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-5108 200 mg BID (Panel 1)<br>Participants receive 200 mg of MK-5108 orally twice daily (BID) the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 400 mg BID (Panel 1)<br>Participants receive 400 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 800 mg BID (Panel 1)<br>Participants receive 800 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 1200 mg BID (Panel 1)<br>Participants receive 1200 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 1500 mg BID (Panel 1)<br>Participants receive 1500 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 1800 mg BID (Panel 1)<br>Participants receive 1800 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed). | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>|
| Experimental: MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2)<br>Participants receive 100 mg of MK-5108 orally BID in combination with 60 mg/m^2 Docetaxel administered intravenously (IV) the first 2 days of a 21-day cycle. | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>Drug: docetaxel<br>* Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m^2 Q12H during the first 2 days of each 21-day cycle.<br>* Other names: Taxotere;|
| Experimental: MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2)<br>Participants receive 150 mg of MK-5108 orally BID in combination with 60 mg/m^2 Docetaxel administered IV the first 2 days of a 21-day cycle. | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>Drug: docetaxel<br>* Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m^2 Q12H during the first 2 days of each 21-day cycle.<br>* Other names: Taxotere;|
| Experimental: MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2)<br>Participants receive 150 mg of MK-5108 orally BID in combination with 60 mg/m^2 Docetaxel administered IV the first 2 days of a 21-day cycle. | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>Drug: docetaxel<br>* Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m^2 Q12H during the first 2 days of each 21-day cycle.<br>* Other names: Taxotere;|
| Experimental: MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover)<br>After receiving treatment in Panel 1, one participant crossed over to Panel 2 per protocol following disease progression to receive 100 mg of MK-5108 orally BID in combination with 60 mg/m^2 Docetaxel administered IV the first 2 days of a 21-day cycle. | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>Drug: docetaxel<br>* Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m^2 Q12H during the first 2 days of each 21-day cycle.<br>* Other names: Taxotere;|
| Experimental: MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover)<br>After receiving treatment in Panel 1, participants crossed over to Panel 2 per protocol following disease progression to receive 150 mg of MK-5108 orally BID in combination with 60 mg/m^2 Docetaxel administered IV the first 2 days of a 21-day cycle. | Drug: MK-5108<br>* MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.<br>Drug: docetaxel<br>* Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m^2 Q12H during the first 2 days of each 21-day cycle.<br>* Other names: Taxotere;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Day 1 to Day 21 of study treatment (Cycle 1 for Panel 1, Panel 2, or Crossover) |