A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)
Condition: Locally Advanced, Metastatic Solid Tumors
MeSH terms: Neoplasms
Intervention: MK-2206; docetaxel; erlotinib; carboplatin; paclitaxel; corticosteroid
Intervention description: MK-2206 given by mouth (PO) on Days 1, 3, 5, and 7 of each 21-day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 PO on Day 1 of each 21-day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg); Administered as an IV infusion on Day 1 of each 21-day cycle; Administered daily (QD) PO in each 21-day cycle; Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle; Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle; Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle
Intervention MeSH terms: Paclitaxel; Docetaxel; Carboplatin; Erlotinib Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tumors, cancer

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.

      The primary hypotheses are that administration of MK-2206 in combination with either
      carboplatin + paclitaxel, docetaxel, or erlotinib in participants with locally advanced or
      metastatic solid tumors will have acceptable tolerability, a dose limiting toxicity (DLT)
      rate of ≤30%, plasma exposure and pharmacodynamics that exceed target thresholds, and allow
      for definition of a maximum tolerated dose (MTD) in each of the 3 combinations.
    

Eligibility criteria:

        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.