This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients with locally advanced unresectable or metastatic renal cell carcinoma (RCC).
In this randomized, Phase 3, double-blind, placebo-controlled study, patients will be randomized 2:1 to receive either a combination of pazopanib plus abexinostat or pazopanib plus placebo. At the time of disease progression, patient treatment assignment will be unblinded, and those patients randomized to the pazopanib plus placebo treatment arm will have the option of crossing over to receive treatment with a combination of pazopanib plus abexinostat. After providing written informed consent, patients will be screened for study eligibility within 28 days before their first dose of study drug. After screening assessments, patients who are eligible for inclusion in the study will be randomized and receive their first dose of study drug on Cycle 1 Day 1 (C1D1), within 7 days of randomization. A treatment cycle is 28 days in length. Patients may continue to receive study drug until any of the following events: the development of IRC-verified radiographic progression as assessed by RECIST version 1.1, clinical disease progression, unacceptable toxicity, another discontinuation criterion is met, withdrawal of consent, or closure of the study by the sponsor. No maximum duration of therapy has been set.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
413
All patients will receive pazopanib at a starting dose of 800 mg by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle. Patients should be instructed to take their once- daily oral dose of pazopanib at the same time each morning. Each dose of pazopanib should be taken with an 8 oz/240 mL glass of water either 1 hour before or 2 hours after a meal. Patients should be instructed to swallow the tablets whole and not chew them.
The starting dose and schedule of abexinostat will be 80 mg p.o. BID on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Each dose of abexinostat should be taken with an 8 oz/240 mL glass of water at least half an hour before meals or more than 2 hours after a meal and must be 4 hours apart. Patients should be instructed to swallow the tablets whole and not chew them.
Progression-free survival (PFS)
To compare the PFS between treatment arms. PFS is defined as the time (month) interval between date of randomization and date of radiographic disease progression or death for those without prior evidence of progression, as assessed by blinded Independent Review Committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
PFS by investigator assessment according to RECIST version 1.1.
To compare the PFS between treatment arms by investigator assessment. PFS is defined as the time (month) interval between date of randomization and date of radiographic disease progression or death for those without prior evidence of progression, as assessed by IRC according to RECIST version 1.1.
Time frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
Overall survival (OS)
OS is defined as the interval between date of randomization and date of death. The main objective was to compare the OS between treatment arms by investigator assessment.
Time frame: From progression or end of study, every 3 months follow up until death, patient withdrawal from study follow-up, or study closure, whichever occurs first (up to approximately 4 years).
Adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5
To characterize the safety profile of pazopanib in combination with abexinostat.
Time frame: From Day 1 until end of treatment visit (up to approximately 4 years).
Objective response rate (ORR)
ORR is defined as the proportion of patients with objective evidence of CR or PR by RECIST version 1.1. The main objective was to compare the ORR between treatment arms by investigator assessment.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The starting dose and schedule of abexinostat matching placebo will be 80 mg p.o. BID on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Each dose of placebo should be taken with an 8 oz/240 mL glass of water at least half an hour before meals or more than 2 hours after a meal and must be 4 hours apart. Patients should be instructed to swallow the tablets whole and not chew them.
University Of UA Cancer Center(UACC)/DH-SJHMC
Phoenix, Arizona, United States
WITHDRAWNUniversity of California Davis Comprehensive Cancer Center
Sacramento, California, United States
WITHDRAWNUCSF Helen Diller Family Comphrensive Cancer Center - Hemato
San Francisco, California, United States
WITHDRAWNNorton Cancer Institute, Norton Healthcare Pavilion
Louisville, Kentucky, United States
COMPLETEDOchsner Clinic Foundation
New Orleans, Louisiana, United States
COMPLETEDGU Research Network/Urology Cancer Center
Omaha, Nebraska, United States
WITHDRAWNNebraska Cancer Specialists
Omaha, Nebraska, United States
COMPLETEDNorthwell Health/Monter Cancer Center
Lake Success, New York, United States
WITHDRAWNMainstreet Physicans Care
Rochester, New York, United States
COMPLETEDPrecision Cancer Research/Dayton Physicians Network - Treatment
Kettering, Ohio, United States
WITHDRAWN...and 28 more locations
Time frame: Screening, Cycle 3 Day 1 (C3D1), Cycle 5 Day 1 (C5D1), Cycle 7 Day 1 (C7D1), and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).
Duration of response (DOR)
DOR is defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause by RECIST version 1.1. The main objective was to compare the DOR between treatment arms by investigator assessment.
Time frame: Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).
ORR by RECIST version 1.1 in cross-over patient population
To describe the ORR in patients who cross over to receive pazopanib plus abexinostat at the time of disease progression on pazopanib monotherapy by investigator assessment.
Time frame: Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).
DOR by RECIST version 1.1 in cross-over patient population
To describe the DOR in patients who cross over to receive pazopanib plus abexinostat at the time of disease progression on pazopanib monotherapy by investigator assessment.
Time frame: Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).
Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) scores
To assess the impact of pazopanib with or without abexinostat on disease-related symptoms and health-related quality of life (QoL) by investigator assessment. QoL will be assessed by measuring change from baseline in FKSI-19. The FKSI-19 assesses disease-related symptoms experienced in the past 7 days. Patients are asked to respond to 12 questions ("I have a lack of energy," "I feel pain," for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 48).
Time frame: First day of treatment Cycle1, Cycle 2, Cycle 6 (each cycle is 28 days in length) until end-of-treatment visit (up to approximately 4 years).
Mean change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT-F) scores
To assess the impact of pazopanib with or without abexinostat on disease-related symptoms and QoL by investigator assessment. QoL will be assessed by measuring change from baseline in FACIT-F. The FACIT-F scale measures QoL experienced in the past seven days. The measurement consisted of 5 domains (physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns) assessed on a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much).
Time frame: First day of treatment Cycle1, Cycle 2, Cycle 6 (each cycle is 28 days in length) and at end-of-treatment visit (up to approximately 4 years).