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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.

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.

Condition or disease Intervention/treatment Phase
Renal Cell Cancer Drug: Pembrolizumab Pre-Resection Procedure: Surgical Resection Drug: Pembrolizumab Post-Resection Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 3, 2014
Actual Primary Completion Date : July 5, 2019
Actual Study Completion Date : July 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

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.
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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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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 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

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): NCT02212730


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02212730    
Other Study ID Numbers: 3475-031
2014-002526-12 ( EudraCT Number )
MK-3475-031 ( Other Identifier: Merck )
KEYNOTE-031 ( Other Identifier: Merck )
First Posted: August 8, 2014    Key Record Dates
Results First Posted: July 16, 2020
Last Update Posted: July 16, 2020
Last Verified: June 2020
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 Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents