A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)
Condition: Locally Advanced or Metastatic Solid Tumors
MeSH terms: Neoplasms
Intervention: MK-2206; AZD6244
Intervention description: Oral tablets; Oral capsules
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will investigate the safety and tolerability of combination therapy with MK-2206
      and AZD6244 (selumetinib) 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.

      The primary hypotheses for this study are that: 1) the Dose-limiting Toxicities (DLTs)
      observed in participants with locally advanced or metastatic solid tumors after
      administration of combination therapy with MK-2206 and AZD6244 will be dose-dependent and
      allow for identification of the MTD, and 2) oral administration of combination therapy with
      MK-2206 and AZD6244 to participants with advanced solid tumors will be generally
      well-tolerated.
    

Eligibility criteria:

        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