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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00880568
First received: April 10, 2009
Last updated: October 29, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Neoplasms
Malignant
Drug: MK-1496
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of MK1496 in Patients With Advanced Solid Tumor

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (up to 21 or 28 days, depending on treatment arm) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Any Clinical or Laboratory Adverse Event [ Time Frame: First dose up to 30 days after last dose (up to 2 years) ] [ Designated as safety issue: Yes ]
    This is a measure of the number of participants who experienced any adverse event (AE) while on study.


Secondary Outcome Measures:
  • Area Under the Curve From Hour 0 to Hour 24 (AUC[0-24]) for MK-1496 Single Dose (21-Day Cycle) [ Time Frame: Cycle 1, Day 1 (Hour 0 through Hour 24) ] [ Designated as safety issue: No ]

    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.


  • Mean AUC[0-24] of MK-1496 on Day 1 of Multiple Dose Administration (28-Day Cycle) [ Time Frame: Cycle 1, Day 1 (Hour 0 through Hour 24) ] [ Designated as safety issue: No ]

    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.


  • Mean AUC[0-24] of MK-1496 on Day 3 of Multiple Dose Administration (28-Day Cycle) [ Time Frame: Cycle 1, Day 3 (Hour 0 through Hour 24) ] [ Designated as safety issue: No ]

    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.



Enrollment: 27
Study Start Date: April 2009
Study Completion Date: January 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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
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 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 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 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 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 Days 1 and 3 each week for 3 weeks (Days 1, 3, 8, 10, 15 and 17) of each 28-day cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00880568     History of Changes
Other Study ID Numbers: MK-1496-002, 2009_575
Study First Received: April 10, 2009
Results First Received: September 25, 2012
Last Updated: October 29, 2012
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 15, 2014