A Study of MK-4827 in Combination With Standard Chemotherapy in Participants With Advanced Solid Tumors (MK-4827-008 AM1)

Study Overview
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Brief Summary
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This study will find the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RPTD) of MK4827 when administered in combination with standard doses of carboplatin, or carboplatin/paclitaxel, or carboplatin/liposomal doxorubicin in the treatment of advanced solid cancers in adults.

Detailed Description
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The decision to discontinue new enrollment is not related to any concerns about the safety profile of the product.

Official Title
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A Phase Ib Dose Escalation Study of MK-4827 in Combination With Carboplatin, Carboplatin/Paclitaxel and Carboplatin/Liposomal Doxorubicin in Patients With Advanced Solid Tumors

Conditions
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Cancer: Solid Tumors

Intervention / Treatment
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* Drug: MK-4827
* Drug: carboplatin
* Drug: paclitaxel
* Drug: liposomal doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has a locally advanced or metastatic solid tumor for which carboplatin, carboplatin/paclitaxel, or carboplatin/liposomal doxorubicin are the standard of care. Participant has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. Exclusion Criteria: Participant has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to entering the study. Participant has had more than two prior lines of chemotherapy. Participant has known central nervous system metastases or a primary central nervous system tumor. Participant is pregnant or breastfeeding or expecting to conceive during the timeframe of the study. Participant is known to be human immunodeficiency virus (HIV) positive. Participant has a history of Hepatitis B or C. Participant has a symptomatic pleural effusion. Participant with a left ventricular ejection fraction (LVEF) below the institutional norm, or with prior exposure to doxorubicin is not eligible for the MK4827 + carboplatin/liposomal doxorubicin study arm.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-4827 + carboplatin<br> | Drug: MK-4827<br>* Capsules, orally, once daily, on Days 1 and 3 of each 21- or 28-day Cycle, at the assigned dose level, starting at 40 mg per dose.<br>Drug: carboplatin<br>* Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle<br>|
| Experimental: MK-4827 + carboplatin/paclitaxel<br> | Drug: MK-4827<br>* Capsules, orally, once daily, on Days 1 and 3 of each 21- or 28-day Cycle, at the assigned dose level, starting at 40 mg per dose.<br>Drug: carboplatin<br>* Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle<br>Drug: paclitaxel<br>* Intravenous infusion, 175 mg/m2, once, on Day 3 of each 21-day cycle<br>|
| Experimental: MK-4827 + carboplatin/liposomal doxorubicin<br> | Drug: MK-4827<br>* Capsules, orally, once daily, on Days 1 and 3 of each 21- or 28-day Cycle, at the assigned dose level, starting at 40 mg per dose.<br>Drug: carboplatin<br>* Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle<br>Drug: liposomal doxorubicin<br>* Intravenous infusion, 30 mg/m2, once, on Day 3 of each 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) |  | Each cycle (21 or 28 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinical and laboratory adverse events (AEs) |  | Baseline to 30 days post last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Solid Tumors