A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)
A Phase I Study of Oral MK-2206 in Combination With Oral AZD6244 in Patients With Locally Advanced or Metastatic Solid Tumors
2 other identifiers
interventional
63
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2009
Longer than P75 for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 23, 2009
CompletedFirst Submitted
Initial submission to the registry
November 25, 2009
CompletedFirst Posted
Study publicly available on registry
November 30, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 26, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
July 16, 2014
CompletedResults Posted
Study results publicly available
August 7, 2018
CompletedAugust 7, 2018
November 1, 2017
3 years
November 25, 2009
November 3, 2017
November 3, 2017
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants With a Dose-limiting Toxicity (DLT)
Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. DLTs included: Grade 4 neutropenia lasting for ≥7 days; Grade 3 or Grade 4 neutropenia with fever \>38.5ºC and/or infection requiring antibiotic or anti-fungal treatment; Grade 4 thrombocytopenia (≤25.0 x 10\^9/L); Grade ≥3 non-hematologic toxicity with exceptions; Any drug-related AE, regardless of CTCAE Grade, leading to a dose modification of MK-2206 or AZD6244; Unresolved CTCAE Grade ≥3 drug-related toxicity requiring drug interruption for \>14 days; ≥ Grade 3 signs or symptoms of glucose intolerance and accompanied by ≥ Grade 2 hyperglycemia (glucose \>160 dL or 8.9 mmol/L); ≥ Grade 3 electrolyte abnormalities due to glucose intolerance and not attributable to another cause; Diagnosis of lactoacidosis or ketoacidosis; Persistent increases in corrected QT (QTc) interval (\>60 msec from baseline and/or \>500 msec); Clinically significant bradycardia.
Cycle 1 (Up to 28 days)
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE. The number of participants who experienced at least one AE is presented.
Up to approximately 23 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Up to approximately 20 months
Secondary Outcomes (1)
Number of Participants With a Tumor Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression (Up to 2 years)
Study Arms (9)
MK-2206 45 mg QOD + AZD6244 75 mg QD
EXPERIMENTALParticipants 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.
MK-2206 45 mg QOD + AZD6244 75 mg BID
EXPERIMENTALParticipants 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.
MK-2206 90 mg QW + AZD6244 50 mg BID
EXPERIMENTALParticipants 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.
MK-2206 90 mg QW + AZD6244 75 mg QD
EXPERIMENTALParticipants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules QD starting on Day 1 of each 28-day cycle.
MK-2206 90 mg QW + AZD6244 75 mg BID
EXPERIMENTALParticipants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules BID starting on Day 1 of each 28-day cycle.
MK-2206 90 mg QW + AZD6244 100 mg QD
EXPERIMENTALParticipants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
MK-2206 90 mg QW + AZD6244 150 mg QD
EXPERIMENTALParticipants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 150 mg oral capsules QD starting on Day 1 of each 28-day cycle.
MK-2206 100 mg QW + AZD6244 100 mg QD
EXPERIMENTALParticipants receive MK-2206 100 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
MK-2206 135 mg QW + AZD6244 100 mg QD
EXPERIMENTALParticipants receive MK-2206 135 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
Interventions
Oral tablets
Oral capsules
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLClead
- AstraZenecacollaborator
Related Publications (1)
Tolcher AW, Khan K, Ong M, Banerji U, Papadimitrakopoulou V, Gandara DR, Patnaik A, Baird RD, Olmos D, Garrett CR, Skolnik JM, Rubin EH, Smith PD, Huang P, Learoyd M, Shannon KA, Morosky A, Tetteh E, Jou YM, Papadopoulos KP, Moreno V, Kaiser B, Yap TA, Yan L, de Bono JS. Antitumor activity in RAS-driven tumors by blocking AKT and MEK. Clin Cancer Res. 2015 Feb 15;21(4):739-48. doi: 10.1158/1078-0432.CCR-14-1901. Epub 2014 Dec 16.
PMID: 25516890RESULT
MeSH Terms
Interventions
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 25, 2009
First Posted
November 30, 2009
Study Start
November 23, 2009
Primary Completion
November 26, 2012
Study Completion
July 16, 2014
Last Updated
August 7, 2018
Results First Posted
August 7, 2018
Record last verified: 2017-11