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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01294735
First received: February 10, 2011
Last updated: August 14, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Recurrence of Solid Tumor
Glioblastoma Multiforme
Melanoma
Drug: MK-4827
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of MK-4827 in Combination With Temozolomide in Patients With Advanced Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with DLTs [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • Number of participants with 6-month progression-free survival [ Time Frame: 6 months from baseline imaging ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ Time Frame: First dose to progressive disease or death, whichever occurs first ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: February 2011
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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.
  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: NCT01294735     History of Changes
Other Study ID Numbers: 4827-014
Study First Received: February 10, 2011
Last Updated: August 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Temozolomide
glioblastoma multiforme
melanoma
advanced neoplasm

Additional relevant MeSH terms:
Glioblastoma
Melanoma
Recurrence
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroendocrine Tumors
Nevi and Melanomas
Disease Attributes
Pathologic Processes
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014