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

NCT ID: NCT00848718

Last Updated: 2019-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-17
• Study Completion Date: 2012-05-17

Brief 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.

Conditions

Locally Advanced, Metastatic Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-2206 + carboplatin + paclitaxel

MK-2206 combined with carboplatin and paclitaxel

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

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)

carboplatin

Intervention Type: DRUG

Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

paclitaxel

Intervention Type: DRUG

Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

MK-2206 + docetaxel

MK-2206 combined with docetaxel plus pretreatment with a corticosteroid

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

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)

docetaxel

Intervention Type: DRUG

Administered as an IV infusion on Day 1 of each 21-day cycle

corticosteroid

Intervention Type: DRUG

Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle

MK-2206 + erlotinib

MK-2206 combined with erlotinib

Group Type: EXPERIMENTAL

MK-2206

Intervention Type: DRUG

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)

erlotinib

Intervention Type: DRUG

Administered daily (QD) PO in each 21-day cycle

Interventions

MK-2206

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)

Intervention Type: DRUG

docetaxel

Administered as an IV infusion on Day 1 of each 21-day cycle

Intervention Type: DRUG

erlotinib

Administered daily (QD) PO in each 21-day cycle

Intervention Type: DRUG

carboplatin

Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

Intervention Type: DRUG

paclitaxel

Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

Intervention Type: DRUG

corticosteroid

Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle

Intervention Type: DRUG

Other Intervention Names

Taxotere®; Tarceva®; Paraplatin®; Taxol®

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Molife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1.

Reference Type: DERIVED

PMID: 24387695 (View on PubMed)

Other Identifiers

2009_547

Identifier Type: -

Identifier Source: secondary_id

MK-2206-003

Identifier Type: OTHER

Identifier Source: secondary_id

2206-003

Identifier Type: -

Identifier Source: org_study_id