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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Locally Advanced, Metastatic Solid Tumors

Treatments: Drug: docetaxel; Drug: corticosteroid; Drug: MK-2206; Drug: paclitaxel; Drug: carboplatin; Drug: erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00848718

2206-003

2009_547

MK-2206-003 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 77 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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77 participants in 3 patient groups

MK-2206 + carboplatin + paclitaxel

Experimental group

Description:

MK-2206 combined with carboplatin and paclitaxel

Treatment:

Drug: MK-2206

Drug: paclitaxel

Drug: carboplatin

MK-2206 + docetaxel

Experimental group

Description:

MK-2206 combined with docetaxel plus pretreatment with a corticosteroid

Treatment:

Drug: corticosteroid

Drug: MK-2206

Drug: docetaxel

MK-2206 + erlotinib

Experimental group

Description:

MK-2206 combined with erlotinib

Treatment:

Drug: erlotinib

Drug: MK-2206