A Study of MK-2206 in Combination With Trastuzumab and Lapatinib for the Treatment of HER2+ Solid Tumors (MK-2206-015)
Condition: Advanced Solid Tumors; Breast Cancer
MeSH terms: Neoplasms
Intervention: MK-2206; Trastuzumab; Lapatinib
Intervention description: [Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.; Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.; Lapatinib tablets will be administered orally QD in doses of 500 mg, 750 mg, or 1000 mg.
Intervention MeSH terms: Trastuzumab; Lapatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Documented to be HER2+

Summary:

      This study will assess the safety, tolerability, and the maximum tolerated dose (MTD) of
      MK-2206 in combination with both trastuzumab and trastuzumab/lapatinib in participants with
      human epidermal growth factor receptor 2 positive (HER2+) breast cancer and other solid
      tumors. The primary hypothesis of this study is that the combination of oral MK-2206 with
      trastuzumab or with trastuzumab/lapatinib will be well tolerated in participants with
      advanced HER2+ solid tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a histologically or cytologically-confirmed locally advanced or metastatic HER2+
             solid tumor.

          -  Have performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Have adequate organ function.

          -  Female participants have a negative pregnancy test 72 hours prior to receiving the
             first dose of study medication.

          -  Have completed any major surgery for a minimum of 28 days prior to enrollment in this
             study.

          -  Able to swallow tablets and has no surgical or anatomical condition that will preclude
             the patient from swallowing or absorbing oral medications on an ongoing basis.

        Exclusion Criteria:

          -  Had chemotherapy, radiotherapy or biological therapy within 4 weeks of screening.
             Participants receiving trastuzumab and/or lapatinib prior to screening must be off
             both medications for 1 week prior to first dose of MK-2206 if trastuzumab had been
             administered at 2 mg/kg weekly and 3 weeks if trastuzumab had been administered at 6
             mg/kg weekly.

          -  Currently participating or has participated in a study with an investigational
             compound or device within 30 days, or 5x half-life from prior agents, whichever is
             longer, of Day 1 of this study

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has a primary CNS tumor.

          -  Has known hypersensitivity to the components of study drugs or its analogs.

          -  Has a history or evidence of heart disease.

          -  Has uncontrolled hypertension or diabetes.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding or is expecting to conceive or father children during the
             study.

          -  Is HIV positive.

          -  Has symptomatic ascites or pleural effusion.

          -  Is receiving treatment with oral corticosteroids for reason other than CNS metastasis.