Recurrence of Solid TumorPhase 1NCT01294735
Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Cancer (MK-4827-014 AM1)
A Phase 1 study testing MK-4827 and Temozolomide in people with Recurrence of Solid Tumor and Glioblastoma Multiforme, run by Merck Sharp & Dohme LLC.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrence of Solid Tumor, Glioblastoma Multiforme, Melanoma
- What is being tested?
- MK-4827 and Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- Feb 2011to May 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: 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.
- Conditions
- Recurrence of Solid Tumor, Glioblastoma Multiforme, Melanoma
- Being tested
- MK-4827, Temozolomide
- Keywords
- Temozolomide, glioblastoma multiforme, melanoma, advanced neoplasm
- Medical subject headings
- Glioblastoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A, MK-4827 + temozolomide dose escalation cohort | Experimental | Not described Receives: Drug: MK-4827; Drug: Temozolomide |
| Part B, MK-4827 + temozolomide melanoma cohort | Experimental | Not described Receives: Drug: MK-4827; Drug: Temozolomide |
| Part B, MK-4827 + temozolomide glioblastoma multiforme cohort | Experimental | Not described Receives: Drug: MK-4827; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with DLTs
Measured: Cycle 1 (28 days)
Secondary outcomes (3)
Number of participants with an objective response rate of partial or complete response
Measured: 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
Measured: 6 months from baseline imaging
Progression-Free Survival (PFS)
Measured: First dose to progressive disease or death, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionApr 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrence of Solid TumorStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01294735
- Sponsor's protocol ID
- 4827-014
- Status last verified
- Aug 2012
- First submitted
- 10 Feb 2011
- Last updated
- 15 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of MK-4827 in Combination With Temozolomide in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01294735
- Acronym / sponsor ID
- 4827-014
- Conditions
- Recurrence of Solid Tumor, Glioblastoma Multiforme, Melanoma
- Keywords
- Temozolomide, glioblastoma multiforme, melanoma, advanced neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 11 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A, MK-4827 + temozolomide dose escalation cohort | Experimental | Drug: MK-4827, Drug: Temozolomide |
| Part B, MK-4827 + temozolomide melanoma cohort | Experimental | Drug: MK-4827, Drug: Temozolomide |
| Part B, MK-4827 + temozolomide glioblastoma multiforme cohort | Experimental | Drug: MK-4827, Drug: Temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-4827MK-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 | Part A, MK-4827 + temozolomide dose escalation cohort, Part B, MK-4827 + temozolomide glioblastoma multiforme cohort, Part B, MK-4827 + temozolomide melanoma cohort |
| TemozolomideMK-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 | Part A, MK-4827 + temozolomide dose escalation cohort, Part B, MK-4827 + temozolomide glioblastoma multiforme cohort, Part B, MK-4827 + temozolomide melanoma cohort |
Primary outcome
Number of participants with DLTs
Time frame: Cycle 1 (28 days)
3 secondary outcomes
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.
Number of participants with 6-month progression-free survival
Time frame: 6 months from baseline imaging
Progression-Free Survival (PFS)
Time frame: First dose to progressive disease or death, whichever occurs first
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-4827 and Temozolomide in people with Recurrence of Solid Tumor and Glioblastoma Multiforme, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with DLTs (time frame: Cycle 1 (28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2012.