A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Locally Advanced or Metastatic Solid Tumors

Treatments: Drug: MK-2206; Drug: AZD6244

Study type: Interventional

Funder types: Industry

Identifiers

NCT01021748

2206-010

2009_698 (Other Identifier)

Details and patient eligibility

About

This study will investigate the safety and tolerability of combination therapy with MK-2206 and AZD6244 (selumetinib) and determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) for this drug combination in the treatment of participants with locally advanced or metastatic solid tumors. Preliminary efficacy data will also be collected.

The primary hypotheses for this study are that: 1) the Dose-limiting Toxicities (DLTs) observed in participants with locally advanced or metastatic solid tumors after administration of combination therapy with MK-2206 and AZD6244 will be dose-dependent and allow for identification of the MTD, and 2) oral administration of combination therapy with MK-2206 and AZD6244 to participants with advanced solid tumors will be generally well-tolerated.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or therapies known to provide clinical benefit, or for whom efficacious standard therapy or any other therapy known to provide clinical benefit does not exist
• Participant has no history of prior cancer, except certain cervical, skin, or prostate cancers, or has undergone potentially curative therapy with no evidence of disease for 5 years
• At least 18 years of age
• Participant is able to swallow oral medications
• For participants enrolled in the MTD expansion cohorts, must have a diagnosis of Kirsten rat sarcoma viral oncogene homolog (KRAS) tumor-type non small-cell lung cancer (NSCLC). Additional tumor types (with specific mutations) may be added to the MTD expansion cohorts after discussion between Sponsor and Investigator

Exclusion criteria

• Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks of entering the study
• Participant is currently participating in or has participated in a study of an investigational compound or device within 30 days or 5x the compound's half-life of Cycle 1, Day 1
• Participant has known central nervous system metastases and/or carcinomatous meningitis
• Participant has a primary central nervous system tumor or spinal cord compression
• Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
• Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
• Participant is human immunodeficiency virus (HIV) positive
• Participant is has history of hepatitis B or C or active hepatitis A
• Participant has a history or current evidence of heart disease
• Participant has uncontrolled high blood pressure
• Participant has poorly controlled diabetes

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 9 patient groups

MK-2206 45 mg QOD + AZD6244 75 mg QD

Experimental group

Description:

Participants receive MK-2206 45 mg oral tablets once every other day (QOD) PLUS AZD6244 75 mg oral capsules once daily (QD) starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 45 mg QOD + AZD6244 75 mg BID

Experimental group

Description:

Participants receive MK-2206 45 mg oral tablets QOD PLUS AZD6244 75 mg oral capsules twice daily (BID) starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 90 mg QW + AZD6244 50 mg BID

Experimental group

Description:

Participants receive MK-2206 90 mg oral tablets once weekly (QW) PLUS AZD6244 50 mg oral capsules BID starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 90 mg QW + AZD6244 75 mg QD

Experimental group

Description:

Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules QD starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 90 mg QW + AZD6244 75 mg BID

Experimental group

Description:

Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules BID starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 90 mg QW + AZD6244 100 mg QD

Experimental group

Description:

Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 90 mg QW + AZD6244 150 mg QD

Experimental group

Description:

Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 150 mg oral capsules QD starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 100 mg QW + AZD6244 100 mg QD

Experimental group

Description:

Participants receive MK-2206 100 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206

MK-2206 135 mg QW + AZD6244 100 mg QD

Experimental group

Description:

Participants receive MK-2206 135 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.

Treatment:

Drug: AZD6244

Drug: MK-2206