Phase I Study of MK-1496 in Patients With Advanced Solid Tumor (MK-1496-002 AM 4)(COMPLETED)

A Phase I Dose Escalation Study of MK1496 in Patients With Advanced Solid Tumor

This study determines recommended clinical dose, to evaluate the safety, tolerability and pharmacokinetics of MK-1496 in patients with locally advanced and/or metastatic solid tumors who have failed standard therapy or for whom no standard therapy exists, in two dosing schedules in Japan.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Malignant
• Intervention / Treatment: Drug: MK-1496; Drug: MK-1496

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Participant must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
• Participant must have Performance Status 0 or 1.
• Participant must have adequate organ function.

Exclusion Criteria

• Participant has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration.
• Participant has received 4 or greater regimens of chemotherapy (adjuvant therapy and incomplete 1 cycle treatment are not considered as 1 regimen).
• Participant has known hypersensitivity to the components of study drug or its analogs.
• Participant has had prescription or non-prescription drugs or other products known to be moderate or potent inhibitors/inducers of cytochrome P (CYP)3A4, or substrates of CYP3A4 with narrow therapeutic window.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MK-1496 20 mg (21-Day Cycle); Participants receiving MK-1496 20 mg on Day 1 of each 21-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 40 mg (21-Day Cycle); Participants receiving MK-1496 40 mg on Day 1 of each 21-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 80 mg (21-Day Cycle); Participants receiving MK-1496 80 mg on Day 1 of each 21-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 120 mg (21-Day Cycle); Participants receiving MK-1496 120 mg on Day 1 of each 21-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 20 mg (28-Day Cycle); Participants receiving MK-1496 20 mg on Days 1, 3, 8, 10, 15, and 17 of each 28-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 40 mg (28-Day Cycle); Participants receiving MK-1496 40 mg on Days 1, 3, 8, 10, 15, and 17 of each 28-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 80 mg (28-Day Cycle); Participants receiving MK-1496 80 mg on Days 1, 3, 8, 10, 15, and 17 of each 28-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 100 mg (28-Day Cycle); Participants receiving MK-1496 100 mg on Days 1, 3, 8, 10, 15, and 17 of each 28-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle
EXPERIMENTAL: MK-1496 120 mg (28-Day Cycle); Participants receiving MK-1496 120 mg on Days 1, 3, 8, 10, 15, and 17 of each 28-day cycle	Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Day 1 of each 21-day cycle; Drug: MK-1496; MK-1496 (20 to 120 mg), orally, administered on Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs)	Dose-limiting toxicities (DLTs) are any adverse events that are not clearly related to disease progression including Grade 4 neutropenia, Grade 3 or 4 febrile neutropenia, thrombocytopenic bleeding or Grade 4 thrombocytopenia, and any Grade 3 or 4 non hematologic toxicity. An adverse event (AE) is any unfavorable and unintended change in the structure and function (Clinical AE) or chemistry (Laboratory AE) of the body temporally associated with the use of study product, whether or not considered related to the use of the product.	Cycle 1 (up to 21 or 28 days, depending on treatment arm)
Number of Participants With Any Clinical or Laboratory Adverse Event	This is a measure of the number of participants who experienced any adverse event (AE) while on study.	First dose up to 30 days after last dose (up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Hour 0 to Hour 24 (AUC[0-24]) for MK-1496 Single Dose (21-Day Cycle)	AUC[0-24] is a measure of the total plasma exposure of drug over a 24-hour period after the initial dose; for this analysis AUC was measured on Day 1 of the first 21-day cycle. AUC[0-24] for the 28-day cycle is reported as Outcome Measures 4 and 5.	Cycle 1, Day 1 (Hour 0 through Hour 24)
Mean AUC[0-24] of MK-1496 on Day 1 of Multiple Dose Administration (28-Day Cycle)	AUC is a measure of the total plasma exposure of a drug. For this analysis, AUC was measured just prior to dosing and through 24 hours postdose on Day 1 of Weeks 1, 2, and 3 in Cycle 1. The AUC value presented is the mean AUC for all measurements. AUC[0-24] for the Day 3 doses is reported as Outcome Measure 5.	Cycle 1, Day 1 (Hour 0 through Hour 24)
Mean AUC[0-24] of MK-1496 on Day 3 of Multiple Dose Administration (28-Day Cycle)	AUC is a measure of the total plasma exposure of a drug. For this analysis, AUC was measured just prior to dosing and through 24 hours postdose on Day 3 of Weeks 1, 2, and 3 in Cycle 1. The AUC value presented is the mean AUC for all measurements. AUC[0-24] for the Day 1 doses is reported as Outcome Measure 4.	Cycle 1, Day 3 (Hour 0 through Hour 24)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: April 10, 2009
• First Submitted That Met QC Criteria: April 13, 2009
• First Posted (ESTIMATE): April 14, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 19, 2015
• Last Update Submitted That Met QC Criteria: February 2, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 1496-002; 2009_575