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Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03099161
Recruitment Status : Terminated (The data did not support study endpoints)
First Posted : April 4, 2017
Results First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE March 30, 2017
First Posted Date  ICMJE April 4, 2017
Results First Submitted Date  ICMJE September 7, 2018
Results First Posted Date  ICMJE June 5, 2019
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE June 27, 2017
Actual Primary Completion Date November 24, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
  • Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (up to 21 days) ]
    DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.
  • Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up tp approximately 8 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.
  • Number of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 8 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 21 days ]
Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 8 months ]
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review. The ORR per RECIST 1.1 for participants is presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
Overall Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
Overall response rate is defined as the proportion of subjects in the analysis population who experience complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors Criteria Version 1.1 (RECIST 1.1) and assessed by investigator review
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)
Official Title  ICMJE A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies
Brief Summary The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm
Intervention  ICMJE
  • Drug: preladenant
    Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
    Other Name: MK-3814A
  • Biological: pembrolizumab
    Administered as IV infusion on Day 1 of each 21-day cycle
    Other Names:
    • KEYTRUDA®
    • MK-3475
Study Arms  ICMJE
  • Experimental: Preladenant 25 mg Twice a Day (BID)
    During an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered. Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
    Intervention: Drug: preladenant
  • Experimental: Preladenant 50 mg BID
    During an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was established based on the number of DLTs at each dose level administered. Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
    Intervention: Drug: preladenant
  • Experimental: Preladenant + Pembrolizumab
    During an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles). Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
    Interventions:
    • Drug: preladenant
    • Biological: pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 1, 2018)
10
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2017)
120
Actual Study Completion Date  ICMJE February 21, 2018
Actual Primary Completion Date November 24, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
  • Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
  • Has measurable disease per RECIST 1.1
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Females must not be pregnant
  • Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study therapy, throughout the study period, and for up to 120 days after the last dose of study therapy

Exclusion Criteria:

  • Has disease that is suitable for local treatment administered with curative intent
  • Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
  • Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
  • Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
  • Is currently taking or has taken drugs that interfere with Cytochrome P450 (CYP)3A4 or CYP2C8 or grapefruit and star fruit in diet within 14 days of the first dose of study therapy
  • Is currently taking or has taken proton pump inhibitors within 5 days of the first dose of study therapy
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of the first dose of study therapy
  • Is expected to require any other form of systemic or localized antineoplastic therapy while on study
  • Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
  • Has clinically active central nervous system metastases and/or carcinomatous meningitis
  • History of a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study drug
  • Has an active infection requiring therapy
  • History of interstitial lung disease
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • History of active tuberculosis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has received a live-virus vaccine within 30 days of the first dose of study therapy
  • Has known Human Immunodeficiency Virus (HIV) (HIV 1 or 2 antibodies) and/or known active and acute Hepatitis B or C infections
  • Has known psychiatric or substance abuse disorders that would interfere with the 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
  • Has not fully recovered from any effects of major surgery without significant detectable infection
  • Has had surgery that required general anesthesia within 2 weeks of the first dose of study therapy
  • Has had surgery that required regional/epidural anesthesia within 72 hours of the first dose of study therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03099161
Other Study ID Numbers  ICMJE 3814A-062
MK-3814A-062 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP