Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1)

August 14, 2012 updated by: Merck Sharp & Dohme LLC

A Phase I Study of MK-4827 in Combination With Temozolomide in Patients With Advanced Cancer

This is a non-randomized two-part study of MK-4827 given with temozolomide in participants with advanced cancer. In Part A of the study, the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of MK-4827 when combined with temozolomide will be found by increasing the MK-4827 dose level in successive cohorts. In Part B of the study, participants with advanced glioblastoma multiforme and advanced melanoma will be enrolled to further evaluate the tolerability and efficacy of the MK-4827 + temozolomide combination.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

Part A

  • Participants with histologically-confirmed advanced solid tumors who have failed to respond to standard therapy, or progressed on standard therapy, or for whom standard therapy does not exist.

Part B

  • Participants must have a histologically-confirmed recurrent glioblastoma multiforme (GBM) with radiographic evidence of progression/recurrence of disease, with up to two prior treatment regimens (not including temozolomide or bevacizumab) for their recurrent disease.

OR

  • Participants must have histologically-confirmed recurrent or metastatic melanoma for which the participant has received up to two prior therapies.
  • Participants must not have received prior treatment with cytotoxic chemotherapy including temozolomide, dacarbazine, or PARP inhibitors.

Part A and Part B

  • Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Participants must have adequate organ function.
  • Women of childbearing potential and male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 90 days after the last dose of study drugs.
  • Participant has no history of a prior malignancy with the exception of gliomas (as secondary GBM is allowed), cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or adequately treated localized prostate carcinoma with Prostate-Specific Antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
  • Participant has at least one measurable metastatic or recurrent lesion.

Exclusion criteria

  • Participant has had chemotherapy, radiotherapy, or biological therapy within four weeks prior to study Day 1 (six weeks for nitrosoureas and mitomycin C) or who has not recovered from adverse events due to agents administered more than four weeks earlier.
  • Participants with known symptomatic or progressive Central Nervous System (CNS) metastases and/or carcinomatous meningitis.
  • Participant has prior exposure to PARP inhibitors. Prior exposure to temozolomide is allowed only for participants with GBM, provided it was received in the adjuvant setting with GBM progression after completion of adjuvant temozolomide treatment and a treatment-free interval of ≥ 3 months.
  • Participant has significant or uncontrolled cardiovascular disease, including New York Heart Association (NYHA) Class III-IV heart failure, unstable angina, or a myocardial infarction within the last six months.
  • Participant is breastfeeding.
  • Participant is known to be Human Immunodeficiency Virus (HIV)-positive.
  • Participant has active Hepatitis B or C.
  • Participant has symptomatic ascites or pleural effusion.
  • Participant has a requirement for concurrent treatment with immunosuppressive agents.
  • Participant must not have prior radiation therapy to more than 30% of hte bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy.
  • Participant has had a prior stem cell or bone marrow transplant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part A, MK-4827 + temozolomide dose escalation cohort
Drug: MK-4827
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.
Drug: Temozolomide
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.
EXPERIMENTAL: Part B, MK-4827 + temozolomide melanoma cohort
Drug: MK-4827
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.
Drug: Temozolomide
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.
EXPERIMENTAL: Part B, MK-4827 + temozolomide glioblastoma multiforme cohort
Drug: MK-4827
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.
Drug: Temozolomide
MK-4827 in combination with temozolomide utilizing a number of doses and schedules for both drugs will be explored to determine a preliminary MTD. The preliminary MTD will then be confirmed in participants with melanoma and glioblastoma multiforme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with DLTs
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with an objective response rate of partial or complete response
Time Frame: Baseline, Day 25 of each cycle, within 30 days of last dose, and at 2 month intervals until disease progression or new therapy initiated.
Baseline, Day 25 of each cycle, within 30 days of last dose, and at 2 month intervals until disease progression or new therapy initiated.
Number of participants with 6-month progression-free survival
Time Frame: 6 months from baseline imaging
6 months from baseline imaging
Progression-Free Survival (PFS)
Time Frame: First dose to progressive disease or death, whichever occurs first
First dose to progressive disease or death, whichever occurs first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (ACTUAL)

April 1, 2012

Study Completion (ACTUAL)

May 1, 2012

Study Registration Dates

First Submitted

February 10, 2011

First Submitted That Met QC Criteria

February 10, 2011

First Posted (ESTIMATE)

February 11, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

August 15, 2012

Last Update Submitted That Met QC Criteria

August 14, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4827-014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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