| General information |
| Database: | DB00362 |
| Objective: | Thisphase 1 study assessed the MTD, DLTs, PK, and efficacy of MK2206 in combination with cytotoxic and targeted therapies. |
| Authors: | Molife LR, et al |
| Title: | Phase 1 trial of the oral AKT inhibitor MK2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. |
| Journal: | J Hematol Oncol. |
| Year: | 2014 |
| PMID: | 24387695 |
| Trial Design |
| Clinical Trial Id: | NCT00848718 |
| Agent: | MK2206
|
| Target: | AKT1 protein kinase
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | MK2206+carboplatin/paclitaxel, docetaxel, or erlotinib |
| Study Type: | phase I, multiarm, openlabel, doseescalation study |
| Key Patients Feature: | Patients 18 years or older with confirmed advanced solidtumors were eligible if they had progressed after standard therapy, or if no standard therapy was available forthem; had Eastern Cooperative Oncology Group performance status less than and equal to 1; surgery or chemotherapy within theprevious 4 weeks; less than and equal to 3 prior lines of cytotoxic therapies(arms 1 and 2 only); residual toxicity from prior treatment grade less than and equal to 1; adequate bone marrow, renal, and hepatic function; and fasting serum glucose less than and equal to 1.1¡Á the upperlimit of normal and hemoglobin A1c (HbA1c) less than and equal to 8%. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | MK2206+carboplatin (AUC 6.0)+paclitaxel 200 mg/m2 (arm 1), MK2206+docetaxel 75 mg/m2 (arm 2), MK2206+erlotinib 100 or 150 mg daily (arm 3) |
| Treatment Info: | Advanced solid tumor patients received oral MK2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK2206 135200 mg QW or 90250 mg Q3W were also tested. |
| Primary End Point: | safety and tolerability, DLTs, and the MTD/recommended phase 2 dose (RP2D) |
| Secondary End Point: | the PK profile, antitumor activity and correlation of antitumor activity. |
| Patients Number: | 72 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | MTD of MK2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drugrelated toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, non small cell lung cancer, and cervical cancers. Six patients had stable disease more than and equal to 6 months |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common drugrelated toxicities included fatigue (68%), nausea (49%), and rash (47%). |
| Conclusions: | MK2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was welltolerated, with early evidence of antitumor activity. |