Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02212730
Recruitment Status : Terminated (Terminated early due to low enrollment)
First Posted : August 8, 2014
Results First Posted : July 16, 2020
Last Update Posted : July 16, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE August 6, 2014
First Posted Date  ICMJE August 8, 2014
Results First Submitted Date  ICMJE June 22, 2020
Results First Posted Date  ICMJE July 16, 2020
Last Update Posted Date July 16, 2020
Actual Study Start Date  ICMJE December 3, 2014
Actual Primary Completion Date July 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen [ Time Frame: Up to Week 16 ]
    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 [ Time Frame: Up to 56 weeks ]
    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 [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 6, 2014)
  • Number of participants with an adverse event [ Time Frame: Up to Week 22 ]
  • Number of Participants Who Discontinued Treatment Due to an Adverse Event [ Time Frame: Up to Week 7 ]
  • Percentage of participants treated with pembrolizumab with a 2-fold or greater change from baseline in intratumoral lymphocytic infiltration [ Time Frame: Baseline and Week 7 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2020)
  • Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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 [ Time Frame: Baseline and Week 7 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2014)
  • Change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with pembrolizumab [ Time Frame: Baseline and Week 7 ]
  • Change from baseline in number of T cells in tumors of participants treated with pembrolizumab [ Time Frame: Baseline and Week 7 ]
  • Change from baseline in number of activated T cells in peripheral blood of participants treated with pembrolizumab [ Time Frame: Baseline and up to Week 12 ]
  • Change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with pembrolizumab [ Time Frame: Baseline and Week 7 ]
  • Change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with pembrolizumab [ Time Frame: Baseline and Week 7 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab Pre-Resection
    200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
    Other Names:
    • KEYTRUDA®
    • MK-3475
  • Procedure: Surgical Resection
    Standard of care surgical resection of RCC tumor
  • Drug: Pembrolizumab Post-Resection
    200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
    Other Names:
    • KEYTRUDA®
    • MK-3475
Study Arms  ICMJE
  • Experimental: Neoadjuvant Pembrolizumab + RCC Resection
    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.
    Interventions:
    • Drug: Pembrolizumab Pre-Resection
    • Procedure: Surgical Resection
    • Drug: Pembrolizumab Post-Resection
  • Experimental: RCC Resection
    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.
    Interventions:
    • Procedure: Surgical Resection
    • Drug: Pembrolizumab Post-Resection
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: July 23, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2014)
36
Actual Study Completion Date  ICMJE July 5, 2019
Actual Primary Completion Date July 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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 Not Provided
Removed Location Countries Belgium,   Canada,   Singapore
 
Administrative Information
NCT Number  ICMJE NCT02212730
Other Study ID Numbers  ICMJE 3475-031
2014-002526-12 ( EudraCT Number )
MK-3475-031 ( Other Identifier: Merck )
KEYNOTE-031 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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 June 2020

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