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Trial record 1 of 1 for:    NCT02853331
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Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02853331
First received: July 29, 2016
Last updated: June 8, 2017
Last verified: June 2017
  Purpose

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) in combination with axitinib versus sunitinib monotherapy as a first-line treatment for participants with advanced/metastatic renal cell carcinoma (mRCC).

The primary hypotheses of this study are: 1) The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Progression-Free Survival (PFS) as assessed by blinded independent central imaging review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and 2) the combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Overall Survival (OS).


Condition Intervention Phase
Renal Cell Carcinoma Biological: Pembrolizumab Drug: Axitinib Drug: Sunitinib Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review [ Time Frame: Up to approximately 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 39 months ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Independent Central Imaging Review [ Time Frame: Up to approximately 2 years ]
  • Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by Blinded Independent Central Imaging Review [ Time Frame: Up to approximately 2 years ]
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 39 months ]
  • Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 39 months ]

Estimated Enrollment: 840
Actual Study Start Date: September 16, 2016
Estimated Study Completion Date: January 27, 2020
Estimated Primary Completion Date: January 27, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumag+Axitinib Combination Therapy
Participants receive pembrolizumab 200 mg intravenously every 3 weeks PLUS axitinib 5 mg orally twice daily.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Axitinib
Oral tablet
Other Name: INLYTA®
Active Comparator: Sunitinib Monotherapy
Participants receive sunitinib 50 mg orally once daily for 4 weeks and then are off treatment for 2 weeks.
Drug: Sunitinib
Oral capsule
Other Name: SUTENT®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.
  • Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease.
  • Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist.
  • Has received no prior systemic therapy for advanced RCC.
  • Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
  • If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
  • Demonstrates adequate organ function.
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
  • Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria:

  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization.
  • Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
  • Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
  • Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
  • Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
  • Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
  • Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
  • Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
  • Has known active CNS metastases and/or carcinomatous meningitis.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has known active Hepatitis B or Hepatitis C infection.
  • Has received a live virus vaccine within 30 days of randomization.
  • Has a clinically significant gastrointestinal (GI) abnormality including:
  • Malabsorption, total gastric resection
  • Or any condition that might affect the absorption of orally taken medication
  • Active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
  • Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation
  • Has QT interval corrected for heart rate (QTc) ≥480 msec.
  • Has a history of any of the following cardiovascular conditions within 12 months of randomization:
  • Myocardial infarction
  • Unstable angina pectoris
  • Cardiac angioplasty or stenting
  • Coronary/peripheral artery bypass graft
  • Class III or IV congestive heart failure per New York Heart Association
  • Cerebrovascular accident or transient ischemic attack
  • Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening.
  • Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg.
  • Has evidence of inadequate wound healing.
  • Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
  • Has hemoptysis within 6 weeks prior to randomization.
  • Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
  • Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Has had a prior solid organ transplant.
  • Is 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 drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02853331

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 42 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02853331     History of Changes
Other Study ID Numbers: 3475-426
2016-000588-17 ( EudraCT Number )
163460 ( Registry Identifier: JAPIC-CTI )
Study First Received: July 29, 2016
Last Updated: June 8, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
VEGFR TKI

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Pembrolizumab
Sunitinib
Axitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2017