Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1)
Primary Purpose
Recurrence of Solid Tumor, Glioblastoma Multiforme, Melanoma
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-4827
Temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Recurrence of Solid Tumor focused on measuring Temozolomide, glioblastoma multiforme, melanoma, advanced neoplasm
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part A, MK-4827 + temozolomide dose escalation cohort
Part B, MK-4827 + temozolomide melanoma cohort
Part B, MK-4827 + temozolomide glioblastoma multiforme cohort
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with DLTs
Secondary Outcome Measures
Number of participants with an objective response rate of partial or complete response
Number of participants with 6-month progression-free survival
Progression-Free Survival (PFS)
Full Information
NCT ID
NCT01294735
First Posted
February 10, 2011
Last Updated
August 14, 2012
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01294735
Brief Title
Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1)
Official Title
A Phase I Study of MK-4827 in Combination With Temozolomide in Patients With Advanced Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrence of Solid Tumor, Glioblastoma Multiforme, Melanoma
Keywords
Temozolomide, glioblastoma multiforme, melanoma, advanced neoplasm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A, MK-4827 + temozolomide dose escalation cohort
Arm Type
Experimental
Arm Title
Part B, MK-4827 + temozolomide melanoma cohort
Arm Type
Experimental
Arm Title
Part B, MK-4827 + temozolomide glioblastoma multiforme cohort
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
MK-4827
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with DLTs
Time Frame
Cycle 1 (28 days)
Secondary Outcome Measure Information:
Title
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.
Title
Number of participants with 6-month progression-free survival
Time Frame
6 months from baseline imaging
Title
Progression-Free Survival (PFS)
Time Frame
First dose to progressive disease or death, whichever occurs first
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
12. IPD Sharing Statement
Learn more about this trial
Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1)
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