A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors

Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel

时间窗: Cycle 1 (Up to 21 days)

Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

MTD of MK-2206 Administered QOD in Combination With Docetaxel

时间窗: Cycle 1 (up to 21 days)

Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1

时间窗: Cycle 1 (Up to 21 days)

A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented.

MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel

时间窗: Cycle 1 (up to 21 days)

Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m\^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

MTD of MK-2206 Administered Q3W in Combination With Docetaxel

时间窗: Cycle 1 (up to 21 days)

Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m\^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

MTD of MK-2206 Administered QOD in Combination With Erlotinib

时间窗: Cycle 1 (up to 21 days)

Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib

时间窗: Cycle 1 (up to 21 days)

Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.

Maximum Plasma Concentration of MK-2206 (Cmax)

时间窗: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented.

Time to Maximum Plasma Concentration of MK-2206 (Tmax)

时间窗: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented.

Minimum Plasma Concentration of MK-2206 (Ctrough)

时间窗: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration.

Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)

时间窗: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented.