NCT01294735

Brief Summary

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2011

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2011

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

February 10, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 11, 2011

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
Last Updated

August 15, 2012

Status Verified

August 1, 2012

Enrollment Period

1.2 years

First QC Date

February 10, 2011

Last Update Submit

August 14, 2012

Conditions

Recurrence of Solid TumorGlioblastoma MultiformeMelanoma

Keywords

Temozolomideglioblastoma multiformemelanomaadvanced neoplasm

Outcome Measures

Primary Outcomes (1)

  • Number of participants with DLTs

    Cycle 1 (28 days)

Secondary Outcomes (3)

  • Number of participants with an objective response rate of partial or complete response

    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

    6 months from baseline imaging

  • Progression-Free Survival (PFS)

    First dose to progressive disease or death, whichever occurs first

Study Arms (3)

Part A, MK-4827 + temozolomide dose escalation cohort

EXPERIMENTAL
Drug: MK-4827Drug: Temozolomide

Part B, MK-4827 + temozolomide melanoma cohort

EXPERIMENTAL
Drug: MK-4827Drug: Temozolomide

Part B, MK-4827 + temozolomide glioblastoma multiforme cohort

EXPERIMENTAL
Drug: MK-4827Drug: Temozolomide

Interventions

MK-4827DRUG

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.

Part A, MK-4827 + temozolomide dose escalation cohortPart B, MK-4827 + temozolomide glioblastoma multiforme cohortPart B, MK-4827 + temozolomide melanoma cohort
TemozolomideDRUG

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.

Part A, MK-4827 + temozolomide dose escalation cohortPart B, MK-4827 + temozolomide glioblastoma multiforme cohortPart B, MK-4827 + temozolomide melanoma cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

GlioblastomaMelanoma

Interventions

niraparibTemozolomide

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeuroendocrine TumorsNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

DacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2011

First Posted

February 11, 2011

Study Start

February 1, 2011

Primary Completion

April 1, 2012

Study Completion

May 1, 2012

Last Updated

August 15, 2012

Record last verified: 2012-08