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

Sponsor

Tesaro, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT01110603

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer: Solid Tumors	Drug: MK-4827 Drug: carboplatin Drug: paclitaxel Drug: liposomal doxorubicin	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MK-4827 + carboplatin	Drug: MK-4827 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. Drug: carboplatin Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle
Experimental: MK-4827 + carboplatin/paclitaxel	Drug: MK-4827 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. Drug: carboplatin Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle Drug: paclitaxel Intravenous infusion, 175 mg/m2, once, on Day 3 of each 21-day cycle
Experimental: MK-4827 + carboplatin/liposomal doxorubicin	Drug: MK-4827 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. Drug: carboplatin Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle Drug: liposomal doxorubicin Intravenous infusion, 30 mg/m2, once, on Day 3 of each 28-day cycle

Arm

Intervention/Treatment

Experimental: MK-4827 + carboplatin

Drug: MK-4827

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.

Drug: carboplatin

Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle

Experimental: MK-4827 + carboplatin/paclitaxel

Drug: MK-4827

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.

Drug: carboplatin

Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle

Drug: paclitaxel

Intravenous infusion, 175 mg/m2, once, on Day 3 of each 21-day cycle

Experimental: MK-4827 + carboplatin/liposomal doxorubicin

Drug: MK-4827

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.

Drug: carboplatin

Intravenous infusion, at AUC 5, once, on Day 3 of each 21- or 28-day cycle

Drug: liposomal doxorubicin

Intravenous infusion, 30 mg/m2, once, on Day 3 of each 28-day cycle

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities (DLTs) [Each cycle (21 or 28 Days)]

Secondary Outcome Measures

Number of participants with clinical and laboratory adverse events (AEs) [Baseline to 30 days post last dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.