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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03745989
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: MK-8353 Drug: Selumetinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Open-label Study of MK-8353 in Combination With Selumetinib (MK-5618) in Participants With Advanced/Metastatic Solid Tumors
Actual Study Start Date : February 22, 2019
Estimated Primary Completion Date : June 27, 2022
Estimated Study Completion Date : June 27, 2022

Arm Intervention/treatment
Experimental: MK-8353 and Selumetinib Dose Escalation
Starting Dose (Dose Level [DL] 1): MK-8353 + selumetinib
Drug: MK-8353
Starting Dose (Dose Level [DL] 1): MK-8353

Drug: Selumetinib
Starting Dose (Dose Level [DL] 1): selumetinib
Other Name: MK-5618




Primary Outcome Measures :
  1. Number of Participants with a Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (3-week Cycle) (Up to 3 weeks) ]
    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.

  2. Number of Participants with one or more Adverse Events (AEs) [ Time Frame: Up to approximately 7 months ]
    Percentage of participants who experienced one or more AEs.

  3. Number of Participants with a Study Drug Discontinuations due to an AE [ Time Frame: Up to approximately 6 months ]
    Percentage of participants discontinuing study treatment(s) due to an AE.


Secondary Outcome Measures :
  1. 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. ]
    Area under the plasma concentration-time profile from Time 0 to 24 hours.

  2. 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. ]
    Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.

  3. 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. ]
    Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

  4. 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. ]
    Area under the plasma concentration-time profile from Time 0 to 24 hours.

  5. 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. ]
    Cmin is a measure of the minimum amount of drug in the plasma after the dose is given.

  6. 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. ]
    Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745989


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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United States, Florida
Florida Cancer Specialists ( Site 7000) Recruiting
Sarasota, Florida, United States, 34232
Contact: Study Coordinator    94137799937270      
United States, Texas
Next Oncology ( Site 0001) Recruiting
San Antonio, Texas, United States, 78229
Contact: Study Coordinator    210-595-5670      
Canada, British Columbia
BC Cancer-Vancouver Center ( Site 0011) Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Study Coordinator    6046758000      
Canada, Ontario
Princess Margaret Cancer Centre ( Site 0012) Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Study Coordinator    4169462911      
Switzerland
Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 0020) Recruiting
Bellinzona, Switzerland, 6500
Contact: Study Coordinator    +41918119410      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03745989    
Other Study ID Numbers: 8353-014
MK-8353-014 ( Other Identifier: Merck Protocol Number )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
advanced/metastatic
solid tumors
Selumetinib
Additional relevant MeSH terms:
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Neoplasms