Advanced Kidney Cancer MedDRA version: 19.0 Level: LLT Classification code 10023400 Term: Kidney cancer System Organ Class: 100000004864
Conditions
Interventions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Be > or = 18 years of age on day of signing informed consent - Have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features - Have locally advanced/metastatic disease (i.e., Stage IV RCC per American Joint Committee on Cancer) or have recurrent disease - Have measurable disease per RECIST 1.1 as assessed by the investigator /site radiologist. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions - Have received no prior systemic therapy for advanced RCC - Provide tumor tissue for biomarker analysis - Demonstrate adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 440
Exclusion criteria
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 prior to randomization or radiation therapy within 2 weeks prior to randomization, or who has not recovered (i.e., or = 480 msec - Has a history of any of the following cardiovascular conditions within 12 months of screening: 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) > or = 150 mm Hg and/or diastolic blood pressure (DBP) > or = 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 or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors - Has current use or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers - Has had a prior solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: First Interim Analysis (IA1) - Timing: To be performed after enrollment completion, when all subjects have an opportunity to have at least 4 scheduled scans, and when approximately 50% of the final required OS events (or 198 deaths) have accrued. It is expected to be 21 months after study start. Approximately 380 PFS events are expected at IA1 - Purpose: Final analysis for PFS and IA1 for OS Second Interim Analysis (IA2) - Timing: To be performed when approximately 75% of the final required OS events (or 297 deaths) have accrued, expected to be 29 months after study start - Purpose: IA2 for OS Final analysis - Timing: When approximately 396 deaths have accrued, expected to be 39 months after study start - Purpose: Final analysis for OS (assuming not declared successful at the IA);Main Objective: 1. To evaluate and compare PFS per RECIST 1.1 as assessed by BICR in subjects. treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 2. To evaluate and compare OS in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.;Secondary Objective: 1. To compare ORR and DCR per RECIST 1.1 as assessed by BICR in subjects treated with a combination of pembrolizumab plus axitinib versus sunitinib monotherapy. DOR will also be evaluated. 2. To evaluate and compare safety and tolerability profiles in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 3. To compare time to deterioration (TTD) based on the Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) scale in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy. 4. To assess the longitudinal score changes from baseline to 42 weeks as measured by European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/quality of life scale.;Primary end point(s): - Progression Free Survival (PFS) per RECIST 1.1 as assess | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To compare ORR, DOR and DCR per RECIST 1.1 as assessed by BICR - To evaluate and compare safety and tolerability profiles - To compare time to deterioration (TTD) based on the Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) scale - To assess the longitudinal score changes from baseline to 42 weeks as measured by European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/quality of life scale;Timepoint(s) of evaluation of this end point: - PFS (primary testing), OS, ORR: 21 months (IA1) - OS, ORR: 29 months (IA2) - OS, ORR: 39 months (FA) - The safety endpoint will be evaluated at each IA and at the Final Analysis while the QoL endpoints will be evaluated at Final Analysis - In addition, the DMC will review safety periodically (every 4 months in the first year and frequency may be reduced after one year if no unexpected safety signals occur) - The multiplicity adjustment for these safety reviews will be described in the DMC charter | — |
Countries
Brazil, Canada, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed