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.

November 25, 2009
November 30, 2009
March 23, 2015
November 2009
November 2012   (Final data collection date for primary outcome measure)
Incidence of dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
  • Maximum tolerated dose (MTD) of combination therapy with MK2206 and AZD6244 [ Time Frame: 28 days ]
Complete list of historical versions of study NCT01021748 on Archive Site
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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A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)
A Phase I Study of Oral MK-2206 in Combination With Oral AZD6244 in Patients With Locally Advanced or Metastatic Solid Tumors
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.
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Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Locally Advanced or Metastatic Solid Tumors
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.
Experimental: MK-2206 + AZD6244
Intervention: Drug: MK-2206 plus AZD6244
Tolcher AW, Khan K, Ong M, Banerji U, Papadimitrakopoulou V, Gandara DR, Patnaik A, Baird RD, Olmos D, Garrett CR, Skolnik JM, Rubin EH, Smith PD, Huang P, Learoyd M, Shannon KA, Morosky A, Tetteh E, Jou YM, Papadopoulos KP, Moreno V, Kaiser B, Yap TA, Yan L, de Bono JS. Antitumor activity in RAS-driven tumors by blocking AKT and MEK. Clin Cancer Res. 2015 Feb 15;21(4):739-48. doi: 10.1158/1078-0432.CCR-14-1901. Epub 2014 Dec 16.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
July 2014
November 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
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United Kingdom,   United States
2009_698 ( Other Identifier: Merck Registration Number )
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Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Merck Sharp & Dohme Corp.
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP