A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)

A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors

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.

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.