- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03745989
Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014)
July 25, 2023 updated by: Merck Sharp & Dohme LLC
Phase 1b Open-label Study of MK-8353 in Combination With Selumetinib (MK-5618) in Participants With Advanced/Metastatic Solid Tumors
This is a multicenter, worldwide, open-label study of MK-8353 in combination with selumetinib in participants with histologically or cytologically confirmed diagnosis of advanced solid tumor.
This study will evaluate the safety, tolerability, and exploratory efficacy of MK-8353 in combination with selumetinib.
Study Overview
Detailed Description
As specified by Phase 1 protocol-flexible language, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the trial objectives and/or ensure appropriate safety of the trial participants.
The proposed doses may be adjusted based on evaluation of safety, tolerability, and pharmacokinetic data.
Study Type
Interventional
Enrollment (Actual)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z 4E6
- BC Cancer-Vancouver Center ( Site 0011)
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre ( Site 0012)
-
-
-
-
Ticino
-
Bellinzona, Ticino, Switzerland, 6500
- Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 0020)
-
-
-
-
Florida
-
Sarasota, Florida, United States, 34232
- Florida Cancer Specialists ( Site 7000)
-
-
Texas
-
San Antonio, Texas, United States, 78229
- NEXT Oncology ( Site 0001)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Have a histologically- or cytologically-documented, locally-advanced or metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit.
- Provide an archival or newly obtained tumor tissue sample and blood samples for assessment of proto-oncogene rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF) mutation and for biomarker analysis.
- Have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) as assessed by the investigator/local radiology review.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. (Obtain within 7 days prior to first dose of study treatment.)
- Have the ability to swallow and retain oral medication.
- Demonstrate adequate organ function.
- Male participants must agree to use an acceptable contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period.
- Female participants must not be pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the study's contraceptive guidance during the treatment period and for at least 120 days, after the last dose of study intervention.
Exclusion Criteria:
- Have had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study treatment, or has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs).
- Have clinically active central nervous system metastases and/or carcinomatous meningitis.
- Have an active infection requiring therapy.
- Have known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA).
- Have clinically significant cardiovascular disease as defined by study criteria.
- Have a history of thromboembolic or cerebrovascular events within 6 months prior to treatment start, including transient ischemic attacks (TIAs), cerebrovascular accidents (CVAs), deep vein thrombosis, or pulmonary embolism.
- Have neuromuscular disorders associated with an elevated creatine kinase (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- Have one or more study-defined ophthalmological findings/conditions.
- Have a known history of Gilbert's Syndrome.
- Have a history or current evidence of a gastrointestinal (GI) condition (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications.
- Have a known psychiatric or substance abuse disorder, or any other cognitive disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study treatment.
- Received prior therapy with a mitogen activated protein kinase (MEK) inhibitor (e.g., cobimetinib, trametinib), or an extracellular signal-regulated kinase (ERK) inhibitor (e.g., MK-8353, GCD-0994, ulixertinib), or a proto-oncogene BRAF inhibitor (e.g., dabrafenib, vemurafenib).
- Is currently participating and receiving study treatment in a study of an investigational agent or has participated and received study treatment in a study of an investigational agent or has used an investigational device within 28 days of administration of selumetinib.
- Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents and/or excipients used in the study.
- A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MK-8353 and Selumetinib Dose Escalation
Participants will receive a combination MK-8353 and selumetinib for 4 days on and 3 days off until disease progression or discontinuation.
MK-8353 will be escalated sequentially from 50 mg to 250 mg based on pharmacokinetic and safety data.
Selumetinib will be escalated sequentially from 25 mg to 75 mg based on pharmacokinetic and safety data.
Doses may be adjusted downward sequentially based on tolerability
|
Participants will receive MK-8353 orally twice daily (BID), escalated sequentially from 50 mg to 250 mg.
Participants will receive selumetinib orally BID, escalated sequentially from 25 mg to 75 mg.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Dose Limiting Toxicities
Time Frame: Cycle 1 (3-week Cycle) (Up to 3 weeks)
|
A dose limiting toxicity (DLT) is defined as any hematologic or non-hematologic toxicity ≥Grade 3 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) were considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration.
The number of participants experiencing DLTs was assessed.
|
Cycle 1 (3-week Cycle) (Up to 3 weeks)
|
Number of Participants Experiencing Adverse Events
Time Frame: ~90 days after last treatment dose (up to ~45 weeks)
|
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
The number of participants experiencing AEs was assessed.
|
~90 days after last treatment dose (up to ~45 weeks)
|
Number of Participants Discontinuing Study Treatment Due to AEs
Time Frame: Up to ~33 weeks
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
The number of participants discontinuing study treatment due to AEs was assessed.
|
Up to ~33 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Plasma Concentration-Time Curve for MK-8353 From Time 0 to 12 Hours
Time Frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Blood samples were collected to determine the area under the curve from time 0 to 12 hours (AUC0-12).
AUC is a measure of the amount of drug in the blood over time.
|
Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
AUC0-12 for Selumetinib
Time Frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Blood samples were collected to determine the AUC0-12.
AUC is a measure of the amount of drug in the blood over time.
|
Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Minimum Observed Plasma Concentration for MK-8353
Time Frame: Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
|
Blood samples were collected to determine the minimum observed plasma concentration (Cmin) which is the minimum amount of drug in the plasma after the dose is given.
In cases where Cmin values were below the limit of quantification (BLOQ), arithmetic mean (percent coefficient of variation [%CV]) was reported instead of geometric mean (percent geometric coefficient of variation [%GCV]), since geometric mean (%GCV) was not calculable.
In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."
|
Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
|
Cmin for Selumetinib
Time Frame: Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
|
Blood samples were collected to determine the Cmin which is the minimum amount of drug in the plasma after the dose is given.
In cases where Cmin values were BLOQ, arithmetic mean (%CV) was reported instead of geometric mean (%GCV), since geometric mean (%GCV) was not calculable.
In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."
|
Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
|
Maximum Observed Plasma Concentration for MK-8353
Time Frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Blood samples were collected to determine the maximum observed plasma concentration (Cmax) which is the measure of the maximum amount of drug in the plasma after the dose is given.
|
Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Cmax for Selumetinib
Time Frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Blood samples were collected to determine the Cmax which is the measure of the maximum amount of drug in the plasma after the dose is given.
|
Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 22, 2019
Primary Completion (Actual)
March 19, 2021
Study Completion (Actual)
March 19, 2021
Study Registration Dates
First Submitted
November 16, 2018
First Submitted That Met QC Criteria
November 16, 2018
First Posted (Actual)
November 19, 2018
Study Record Updates
Last Update Posted (Actual)
July 27, 2023
Last Update Submitted That Met QC Criteria
July 25, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 8353-014
- MK-8353-014 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Solid Tumors
-
Incyte CorporationRecruitingA Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid TumorsAdvanced Solid Tumors | Solid Tumors | Metastatic Solid TumorsUnited States, Spain, United Kingdom, France, Italy, Denmark, Switzerland
-
National Cancer Institute (NCI)RecruitingSolid Tumor | Refractory Solid Tumors | Malignant Solid Tumors | Other Neoplasms Solid Tumors | Pediatric Solid TumorUnited States
-
Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
-
Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
-
Hoffmann-La RocheCompletedSolid Tumors, Advanced Solid TumorsUnited States
-
Esperance Pharmaceuticals IncCompletedAdvanced Solid Tumors | Solid TumorsUnited States
-
AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
-
NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
-
Alphamab (Australia) Co Pty Ltd.RecruitingAdvanced Solid Tumors | Metastatic Solid TumorsAustralia
Clinical Trials on MK-8353
-
Merck Sharp & Dohme LLCTerminated
-
Merck Sharp & Dohme LLCCompletedNeoplasms | Colorectal CancerUnited States, Canada
-
Merck Sharp & Dohme LLCCompletedType 2 Diabetes Mellitus
-
Merck Sharp & Dohme LLCCompletedHypertension | Isolated Systolic Hypertension (ISH)
-
Merck Sharp & Dohme LLCTerminated
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCRecruitingHIV | HIV Pre-exposure ProphylaxisUnited States, South Africa, Israel