A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01021748
Recruitment Status : Completed
First Posted : November 30, 2009
Last Update Posted : March 23, 2015
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will investigate the safety and tolerability of combination therapy with MK-2206 and AZD6244 and determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) for this drug combination in the treatment of participants with locally advanced or metastatic solid tumors. Preliminary efficacy data will also be collected.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Solid Tumors Drug: MK-2206 plus AZD6244 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Oral MK-2206 in Combination With Oral AZD6244 in Patients With Locally Advanced or Metastatic Solid Tumors
Study Start Date : November 2009
Actual Primary Completion Date : November 2012
Actual Study Completion Date : July 2014

Arm Intervention/treatment
Experimental: MK-2206 + AZD6244 Drug: MK-2206 plus AZD6244
MK-2206 (tablets) orally, in a once every-other-day (starting dose 45 mg) or once-weekly (starting dose 90 mg) schedule, and AZD6244 (capsules), orally, twice a day (starting dose 75 mg). Doses will be escalated to the MTD.

Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Number of participants with a tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participant has confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or therapies known to provide clinical benefit, or for whom efficacious standard therapy or any other therapy known to provide clinical benefit does not exist
  • Participant has no history of prior cancer, except certain cervical, skin, or prostate cancers, or has undergone potentially curative therapy with no evidence of disease for 5 years
  • At least 18 years of age
  • Participant is able to swallow oral medications
  • For participants enrolled in the MTD expansion cohorts, must have a diagnosis of Kirsten rat sarcoma viral oncogene homolog (KRAS) tumor-type non small-cell lung cancer (NSCLC). Additional tumor types (with specific mutations) may be added to the MTD expansion cohorts after discussion between Sponsor and Investigator

Exclusion Criteria:

  • Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks of entering the study
  • Participant is currently participating in or has participated in a study of an investigational compound or device within 30 days or 5x the compound's half-life of Cycle 1, Day 1
  • Participant has known central nervous system metastases and/or carcinomatous meningitis
  • Participant has a primary central nervous system tumor or spinal cord compression
  • Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
  • Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
  • Participant is human immunodeficiency virus (HIV) positive
  • Participant is has history of hepatitis B or C or active hepatitis A
  • Participant has a history or current evidence of heart disease
  • Participant has uncontrolled high blood pressure
  • Participant has poorly controlled diabetes