A Phase I Study of MK2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (2206-003 AM5)

Tracking Information
First Submitted Date ICMJE	February 19, 2009
First Posted Date ICMJE	February 20, 2009
Last Update Posted Date	January 22, 2015
Study Start Date ICMJE	March 2009
Actual Primary Completion Date	May 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 22, 2010)	Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (One cycle = 21 days) ]; Maximum tolerated dose (MTD) of each of the three combinations [ Time Frame: Cycle 1 (One cycle = 21 days) ]; Maximum plasma concentration of MK-2206 (Cmax) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ]; Time to maximum plasma concentration of MK-2206 (Tmax) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ]; Minimum plasma concentration of MK-2206 (Ctrough) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ]; Area under the MK-2206 concentration versus time curve (AUC) [ Time Frame: Cycle 1 and Cycle 2 (One cycle = 21 days) ]
Original Primary Outcome Measures ICMJE; (submitted: February 19, 2009)	To assess the safety, tolerability and side effects of MK2206 when given in combination with selected chemo and targeted agents in patients with locally advanced or metastatic solid tumors by monitoring of adverse events and clinical/lab measurements. [ Time Frame: 4 weeks ]
Change History	Complete list of historical versions of study NCT00848718 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 22, 2010)	Number of participants who had a tumor response, according to standard RECIST (Response Evaluation Criteria in Solid Tumors) criteria [ Time Frame: Tumor assessments will be performed at baseline and on Day 1 of every other cycle of treatment (every 6 weeks) ]
Original Secondary Outcome Measures ICMJE; (submitted: February 19, 2009)	To explore the anti-tumor activity of MK2206 in combination with either carboplatin + paclitaxel, docetaxel or erlotinib in patients with advanced solid tumors as assessed by imaging and clinical and laboratory evaluations. [ Time Frame: 4 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Phase I Study of MK2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (2206-003 AM5)
Official Title ICMJE	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
Brief Summary	The purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Locally Advanced, Metastatic Solid Tumors
Intervention ICMJE	Drug: MK-2206 combined with carboplatin + paclitaxel MK-2206 given by mouth on days 1, 3, 5, and 7 of the 21 day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 given by mouth on Day 1 of the 21 day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg). On Day 1 of each 21 Day cycle, carboplatin + paclitaxel is given intravenously. Other Name: Paraplatin, Taxol; Drug: MK-2206 combined with docetaxel MK-2206 given by mouth on days 1, 3, 5, and 7 of the 21 day cycle (either 45 mg or 60 mg) (this dosing schedule is no longer enrolling). MK-2206 given by mouth on Day 1 of the 21 day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg). On day 1 of each 21 day cycle, docetaxel is given intravenously. In this treatment arm, an oral corticosteroid is to be taken by mouth every day. Other Name: Taxotere; Drug: MK-2206 combined with erlotinib MK-2206 given by mouth every other day (30 mg, 45 mg or 60 mg) OR MK-2206 given by mouth on Days 1, 8, and 15 of the 21 day cycle (90 mg, 135 mg, or 200 mg). In addition, erlotinib is given daily by mouth in a continuous 21 day cycle for the duration of the study. Other Name: Tarceva
Study Arms	Experimental: MK-2206 + carboplatin + paclitaxel MK-2206 combined with carboplatin and paclitaxel Intervention: Drug: MK-2206 combined with carboplatin + paclitaxel; Experimental: MK-2206 + docetaxel MK-2206 combined with docetaxel Intervention: Drug: MK-2206 combined with docetaxel; Experimental: MK-2206 + erlotinib MK-2206 combined with erlotinib Intervention: Drug: MK-2206 combined with erlotinib
Publications *	Molife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 6, 2012)	72
Original Estimated Enrollment ICMJE; (submitted: February 19, 2009)	130
Actual Study Completion Date	May 2012
Actual Primary Completion Date	May 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria : Participants must have locally advanced or metastatic solid tumors.; Participant is male or female greater than or equal to 18 years of age.; Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale; Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.; Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.; Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing. Exclusion Criteria: Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.; Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.; Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.; Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.; Participant with a primary central nervous system tumor.; Participant has known hypersensitivity to the components of study drug.; Participant has a history or current evidence of heart disease.; Participant has evidence of clinically significant bradycardia (slow heart rate).; Participant has uncontrolled high blood pressure.; Participant at significant risk for hypokalemia (low potassium levels).; Participant is a known diabetic; Participant has known psychiatric or substance abuse disorders.; Participant is a user of illicit drugs.; Participant is pregnant or breastfeeding.; Participant is Human Immunodeficiency Virus (HIV) positive.; Participant has known history of Hepatitis B or C or active Hepatitis A.; Participant has symptomatic ascites or pleural effusion.; Participant is receiving treatment with oral corticosteroids.; Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries	United Kingdom, United States
Administrative Information
NCT Number ICMJE	NCT00848718
Other Study ID Numbers ICMJE	2206-003; 2009_547
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Merck Sharp & Dohme Corp.
Study Sponsor ICMJE	Merck Sharp & Dohme Corp.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Merck Sharp & Dohme Corp.
Verification Date	January 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP