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A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)

Primary Purpose

Renal Cell Cancer

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Pembrolizumab Pre-Resection
Surgical Resection
Pembrolizumab Post-Resection
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Cell Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (>= T1b), not previously treated, and be a candidate for operative tumor resection
  • Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Demonstrate adequate organ function
  • Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
  • Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.

Exclusion Criteria:

  • Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
  • Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
  • Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
  • Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
  • Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
  • Has an active infection requiring systematic therapy
  • Is receiving anticoagulant therapy, with the exception of low dosage aspirin
  • Has severe cardiovascular disease or symptomatic ischemic heart disease
  • Has hepatic decompensation
  • Has uncontrolled thyroid dysfunction
  • Has uncontrolled diabetes mellitus
  • Has known psychiatric or substance abuse disorders
  • Female is pregnant or breastfeeding
  • Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
  • Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
  • Has a known history of human immunodeficiency virus (HIV)
  • Has known active hepatitis B or C
  • Has received a live vaccine within 30 days prior to screening

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Neoadjuvant Pembrolizumab + RCC Resection

    RCC Resection

    Arm Description

    Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.

    Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.

    Outcomes

    Primary Outcome Measures

    Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
    Number of Participants Who Discontinued Treatment Due to an Adverse Event
    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.

    Secondary Outcome Measures

    Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
    Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
    Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
    The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
    Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
    Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.

    Full Information

    First Posted
    August 6, 2014
    Last Updated
    June 22, 2020
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02212730
    Brief Title
    A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)
    Official Title
    A Clinical Trial to Evaluate the Effect of Neoadjuvant MK-3475 (Pembrolizumab) Therapy on Intratumoral Immune Infiltrates in Renal Cell Cancer (RCC) Patients Undergoing Surgical Resection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2020
    Overall Recruitment Status
    Terminated
    Why Stopped
    Terminated early due to low enrollment
    Study Start Date
    December 3, 2014 (Actual)
    Primary Completion Date
    July 5, 2019 (Actual)
    Study Completion Date
    July 5, 2019 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Renal Cell Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    10 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Neoadjuvant Pembrolizumab + RCC Resection
    Arm Type
    Experimental
    Arm Description
    Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.
    Arm Title
    RCC Resection
    Arm Type
    Experimental
    Arm Description
    Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab Pre-Resection
    Other Intervention Name(s)
    KEYTRUDA®, MK-3475
    Intervention Description
    200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
    Intervention Type
    Procedure
    Intervention Name(s)
    Surgical Resection
    Intervention Description
    Standard of care surgical resection of RCC tumor
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab Post-Resection
    Other Intervention Name(s)
    KEYTRUDA®, MK-3475
    Intervention Description
    200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
    Primary Outcome Measure Information:
    Title
    Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
    Description
    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
    Time Frame
    Up to Week 16
    Title
    Number of Participants Who Discontinued Treatment Due to an Adverse Event
    Description
    An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
    Time Frame
    Up to 56 weeks
    Title
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
    Description
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
    Time Frame
    Baseline and Week 7
    Title
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
    Description
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
    Time Frame
    Baseline and Week 7
    Title
    Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
    Description
    The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.
    Time Frame
    Baseline and Week 7
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    Description
    The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
    Time Frame
    Baseline and Week 7
    Title
    Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    Description
    The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
    Time Frame
    Baseline and Week 7
    Title
    Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
    Description
    The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
    Time Frame
    Baseline and Week 7
    Title
    Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    Description
    The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
    Time Frame
    Baseline and Week 7
    Title
    Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
    Description
    The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
    Time Frame
    Baseline and Week 7

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (>= T1b), not previously treated, and be a candidate for operative tumor resection Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Demonstrate adequate organ function Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw. Exclusion Criteria: Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC Has a known additional (other than RCC) malignancy that is progressing or requires active treatment Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis. Has an active infection requiring systematic therapy Is receiving anticoagulant therapy, with the exception of low dosage aspirin Has severe cardiovascular disease or symptomatic ischemic heart disease Has hepatic decompensation Has uncontrolled thyroid dysfunction Has uncontrolled diabetes mellitus Has known psychiatric or substance abuse disorders Female is pregnant or breastfeeding Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway Has a known history of human immunodeficiency virus (HIV) Has known active hepatitis B or C Has received a live vaccine within 30 days prior to screening
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)

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