Clinical Trials /

Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014)

NCT03745989

Description:

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 preliminary efficacy of MK-8353 in combination with selumetinib.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014)
  • Official Title: Phase 1b Open-label Study of MK-8353 in Combination With Selumetinib (MK-5618) in Participants With Advanced/Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 8353-014
  • SECONDARY ID: MK-8353-014
  • NCT ID: NCT03745989

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
MK-8353MK-8353 and Selumetinib Dose Escalation
SelumetinibMK-5618MK-8353 and Selumetinib Dose Escalation

Purpose

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 preliminary efficacy of MK-8353 in combination with selumetinib.

Trial Arms

NameTypeDescriptionInterventions
MK-8353 and Selumetinib Dose EscalationExperimentalStarting Dose (Dose Level [DL] 1): MK-8353 + selumetinib
  • MK-8353
  • Selumetinib

Eligibility Criteria

        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 RAS/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) DNA or
             Hepatitis C Antibody or 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with a Dose Limiting Toxicity (DLT)
Time Frame:Cycle 1 (3-week Cycle) (Up to 3 weeks)
Safety Issue:
Description:The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) will be considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration.

Secondary Outcome Measures

Measure:Area Under the Plasma Concentration-Time Curve (AUC) for MK-8353
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Area under the plasma concentration-time profile from Time 0 to 24 hours.
Measure:Minimum Observed Plasma Concentration (Cmin) for MK-8353
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.
Measure:Maximum Observed Plasma Concentration (Cmax) for MK-8353
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Measure:AUC for Selumetinib
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Area under the plasma concentration-time profile from Time 0 to 24 hours.
Measure:Cmin for Selumetinib
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.
Measure:Cmax for Selumetinib
Time Frame:Study Days 1 and 4 of Cycles 1, 2, and 5 (3-week cycles). For Cycle 1, predose and postdose at 1, 2, 4, 6 minutes, and between 8 and 12 hours; and for Cycles 2 and 5: pre-dose, Hour 1, and Hour 4.
Safety Issue:
Description:Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • advanced/metastatic
  • solid tumors
  • Selumetinib

Last Updated