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Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC) (MK-7690-046)

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ClinicalTrials.gov Identifier: NCT03631407
Recruitment Status : Recruiting
First Posted : August 15, 2018
Last Update Posted : December 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE August 9, 2018
First Posted Date  ICMJE August 15, 2018
Last Update Posted Date December 25, 2018
Actual Study Start Date  ICMJE September 24, 2018
Estimated Primary Completion Date May 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) [ Time Frame: Up to 2 years ]
    ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 criteria.
  • Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to Day 21 of Cycle 1 (each cycle is 21 days) ]
    DLTs are defined as toxicities that: 1) are possibly, probably, or definitely related to study therapy; 2) meet pre-defined severity criteria; and 3) result in a change in the given dose. For each arm, the number of participants experiencing DLTs will be assessed.
  • Adverse Events (AEs) [ Time Frame: Up to 2 years ]
    An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
  • Treatment Discontinuations due to Adverse Events [ Time Frame: Up to 2 years ]
    For each arm, the number of participants discontinuing study treatment due to an AE will be assessed.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03631407 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • Objective Response Rate (ORR) based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST) [ Time Frame: Up to 2 years ]
    A modification of RECIST1.1, iRECIST is adapted to account for the unique tumor response seen with immunotherapeutic drugs. Following initial identification of progressive disease (PD) based on RECIST 1.1, participants who are clinically stable can remain on treatment until PD is confirmed or disconfirmed by iRECIST. For participants where PD is disconfirmed by iRECIST, ORR will be determined, defined as the percentage of participants who achieve a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions).
  • Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS is the time from the first dose of study treatment to the first documented disease progression (per RECIST 1.1 criteria) or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is defined as the time from the first dose of study treatment until death from any cause.
  • Area Under the Concentration vs Time Curve (AUC) of Vicriviroc in Plasma [ Time Frame: At designated time points (up to 6 weeks post-dose) ]
    Plasma vicriviroc concentration will be quantified for each arm to determine AUC, defined as the area under the concentration vs. time curve for vicriviroc.
  • Maximum Observed Plasma Concentration (Cmax) of Vicriviroc [ Time Frame: At designated time points (up to 6 weeks post-dose) ]
    Plasma vicriviroc concentration will be quantified for each arm to determine Cmax, defined as the maximum observed concentration of vicriviroc in plasma.
  • Trough Plasma Concentration (Ctrough) of Vicriviroc [ Time Frame: At designated time points (up to 2 years post-dose) ]
    Plasma vicriviroc concentration will be quantified for each arm to determine Ctrough, defined as the minimum plasma concentration of vicriviroc observed after administration and just before the subsequent dose.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC) (MK-7690-046)
Official Title  ICMJE A Phase 2 Trial to Evaluate the Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)
Brief Summary This trial will evaluate the safety and efficacy of vicriviroc (MK-7690) at 2 dose levels in combination with pembrolizumab (MK-3475) in participants with advanced/metastatic microsatellite stable (MSS) colorectal cancer (CRC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Neoplasms
Intervention  ICMJE
  • Drug: Vicriviroc
    Vicriviroc tablets administered orally, QD at dose level 1 or 2.
  • Biological: Pembrolizumab
    Pembrolizumab administered by IV infusion at 200 mg Q3W, given on cycle day 1.
    Other Names:
    • KEYTRUDA®
    • MK-3475
Study Arms  ICMJE
  • Experimental: Vicriviroc QD at Dose Level 1 + Pembrolizumab
    Participants vicriviroc (dosed orally; once daily [QD]) at dose level 1 in combination with 200 mg pembrolizumab (intravenous [IV] infusion; every 3 weeks [Q3W]) for up to 35 cycles (cycle length: 3 weeks).
    Interventions:
    • Drug: Vicriviroc
    • Biological: Pembrolizumab
  • Experimental: Vicriviroc QD at Dose Level 2 + Pembrolizumab
    Participants receive vicriviroc (dosed orally; QD) at dose level 2 in combination with 200 mg pembrolizumab (IV infusion; Q3W) for up to 35 cycles (cycle length: 3 weeks).
    Interventions:
    • Drug: Vicriviroc
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 13, 2020
Estimated Primary Completion Date May 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a histologically proven locally advanced unresectable or metastatic CRC.
  • Have locally confirmed MSS CRC.
  • Have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan, and have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
  • Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study intervention.
  • Male participants must agree to use contraception and refrain from donating sperm for at least 120 days after the last dose of study intervention.
  • Female participants must be not pregnant and not breastfeeding. Further, a female participant must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention.
  • Have adequate organ function.

Exclusion Criteria:

  • Have a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Have severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study interventions.
  • Have an active autoimmune disease requiring systemic treatment in the past 2 years, except vitiligo or resolved childhood asthma/atopy.
  • Have a history of vasculitis.
  • Have an active infection requiring systemic therapy.
  • Have symptomatic ascites or pleural effusion.
  • Have interstitial lung disease requiring oral or IV glucocorticoids.
  • Have a history of pneumonitis (noninfectious) that required steroids, or has current pneumonitis.
  • Have a known history of HIV infection.
  • Have a known history of hepatitis B or known active hepatitis C virus infection.
  • Have a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study interventions hazardous, or make it difficult to monitor adverse events.
  • Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with study requirements.
  • Are 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 intervention.
  • Are a WOCBP who has a positive urine pregnancy test within 72 hours before randomization or treatment allocation.
  • Have undergone major surgery and have not recovered adequately from any toxicity and/or complications from the intervention before starting study intervention.
  • Have a seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g., CNS malignancy or toxoplasmosis).
  • Have known gastrointestinal (GI) disease such as esophageal, gastric, or duodenal ulceration or inflammatory bowel disease, or history of GI surgery.
  • Are using any drug (therapeutic or recreational), or withdrawal thereof, that poses an increased risk of convulsions.
  • Have had an allogeneic tissue/solid organ transplant.
  • Have received prior therapy with vicriviroc or other CCR5 antagonist (e.g., maraviroc) or have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent.
  • Have been treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
  • Have received prior systemic anticancer therapy, including investigational agents, or has used an investigational device within 28 days before the first dose of study intervention.
  • Have received prior radiotherapy (not to target lesions) within 2 weeks of start of study intervention.
  • Are expected to require any other form of antineoplastic therapy while on study.
  • Have a diagnosis of immunodeficiency, is receiving chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or is taking any other form of immunosuppressive medication within 7 days before the first dose of the study intervention.
  • Have received a live-virus vaccine within 30 days before the first dose of the study intervention.
  • Are currently participating in or have participated in a study of an investigational agent, or have used an investigational device within 28 days before the first dose of study intervention.
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: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03631407
Other Study ID Numbers  ICMJE 7690-046
MK-7690-046 ( 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 December 2018

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