A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)

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ClinicalTrials.gov Identifier: NCT03592472

Recruitment Status : Recruiting

First Posted : July 19, 2018

Last Update Posted : May 12, 2021

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Sponsor:

Information provided by (Responsible Party):

Xynomic Pharmaceuticals, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Drug: Pazopanib Drug: Abexinostat Other: Placebo	Phase 3

Detailed Description:

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	413 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Double (Participant, Investigator)
Masking Description:	This is a double-blind study. The sponsor, investigators, study coordinators, and the patients will be blinded to the study drug (abexinostat/placebo).
Primary Purpose:	Treatment
Official Title:	A Randomized, Phase 3, Double-blind, Placebo-controlled Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma(RENAVIV)
Actual Study Start Date :	July 17, 2018
Estimated Primary Completion Date :	June 30, 2022
Estimated Study Completion Date :	June 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Pazopanib

Genetic and Rare Diseases Information Center resources: Renal Cell Carcinoma Clear Cell Renal Cell Carcinoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pazopanib plus abexinostat Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.	Drug: Pazopanib 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. Other Name: Votrient® Drug: Abexinostat 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. Other Name: PCI-24781
Placebo Comparator: Pazopanib plus placebo Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo 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. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.	Drug: Pazopanib 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. Other Name: Votrient® Other: Placebo 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.

Arm

Intervention/treatment

Experimental: Pazopanib plus abexinostat

Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.

Drug: Pazopanib

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.

Other Name: Votrient®

Drug: Abexinostat

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.

Other Name: PCI-24781

Placebo Comparator: Pazopanib plus placebo

Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo 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. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.

Drug: Pazopanib

Other Name: Votrient®

Other: Placebo

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.

Outcome Measures

Primary Outcome Measures :

Progression-free survival (PFS) [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years). ]
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.

Secondary Outcome Measures :

PFS by investigator assessment 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). ]
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.
Overall survival (OS) [ 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). ]
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.
Adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 [ Time Frame: From Day 1 until end of treatment visit (up to approximately 4 years). ]
To characterize the safety profile of pazopanib in combination with abexinostat.
Objective response rate (ORR) [ 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). ]
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.
Duration of response (DOR) [ 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 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.
ORR by RECIST version 1.1 in cross-over patient population [ 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). ]
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.
DOR by RECIST version 1.1 in cross-over patient population [ 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). ]
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.
Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) scores [ 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). ]
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).
Mean change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT-F) scores [ 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). ]
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).

Eligibility Criteria

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:

To be enrolled in the study, patients will be required to meet all of the following criteria:

Patients aged ≥ 18 years at time of study entry.
Patients have histologically confirmed RCC with clear cell component.
Patients have locally advanced and unresectable or metastatic disease.
Measurable disease as assessed only by the investigator (not verified by IRC) according to RECIST version 1.1.
Patients must not have had any prior vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor treatment in either (neo)adjuvant or locally advanced/metastatic setting. Up to 1 line of prior cytokine or immune checkpoint inhibitor treatment is allowed in either the (neo)adjuvant or metastatic setting provided screening scans indicate progressive disease (PD) during or following completion of treatment.
Patients have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Patients have adequate baseline organ function.
Patients have adequate baseline hematologic function
Patient must be at least 2 weeks from last systemic treatment or dose of radiation prior to date of randomization.

Exclusion Criteria:

Patients who meet any of the following criteria at Screening will not be enrolled in the study:

Has persistent clinically significant toxicities (Grade ≥ 2; per NCI CTCAE version 5 from previous anticancer therapy (excluding alopecia which is permitted and excluding Grades 2 and 3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the investigator, and can be managed with available medical therapies).
Has untreated central nervous system (CNS) metastases. Patients with treated CNS metastases are eligible provided imaging demonstrates no new or progressive metastases obtained at least 4 weeks following completion of treatment. CNS imaging during Screening is not required unless clinically indicated.
Has an additional malignancy requiring treatment within the past 3 years. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, and non-muscle invasive urothelial carcinoma.
Poorly controlled hypertension, defined as systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 100 mmHg. Use of anti-hypertensives and rescreening is permitted.
A new pulmonary embolism or deep venous thrombosis diagnosed within 3 months prior to randomization.
Has a QTcF interval > 480 msec.
New York Heart Association Class III or IV congestive heart failure.
Use of prohibited medication within 7 days or 5 half-lives, whichever is shorter, prior to first dose of study drug.

Contacts and Locations

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): NCT03592472

Contacts

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Contact: Sophia Paspal, Ph.D.	6104055974	sophia.paspal@xynomicpharma.com
Contact: Rahul Aggarwal, M.D.		rahul.aggarwal@ucsf.edu

Locations

Show 38 study locations

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United States, Arizona
University Of UA Cancer Center(UACC)/DH-SJHMC	Withdrawn
Phoenix, Arizona, United States, 85004
United States, California
University of California Davis Comprehensive Cancer Center	Withdrawn
Sacramento, California, United States, 95817
UCSF Helen Diller Family Comphrensive Cancer Center - Hemato	Withdrawn
San Francisco, California, United States, 94158
United States, Kentucky
Norton Cancer Institute, Norton Healthcare Pavilion	Completed
Louisville, Kentucky, United States, 40202
United States, Louisiana
Ochsner Clinic Foundation	Completed
New Orleans, Louisiana, United States, 70121
United States, Nebraska
GU Research Network/Urology Cancer Center	Withdrawn
Omaha, Nebraska, United States, 68130
Nebraska Cancer Specialists	Completed
Omaha, Nebraska, United States, 68130
United States, New York
Northwell Health/Monter Cancer Center	Withdrawn
Lake Success, New York, United States, 11042
Mainstreet Physicans Care	Completed
Rochester, New York, United States, 14642
United States, Ohio
Precision Cancer Research/Dayton Physicians Network - Treatment	Withdrawn
Kettering, Ohio, United States, 45409
United States, Oregon
Oregon Health and Science University	Completed
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital	Completed
Easton, Pennsylvania, United States, 18045
United States, Texas
HOPE Cancer Center of East Texas	Completed
Tyler, Texas, United States, 75701
United States, Washington
Medical Oncology Associates, PS (dba Summit Cancer Centers)	Withdrawn
Spokane, Washington, United States, 99208
China
Beijing Cancer Hospital	Recruiting
Beijing, China, 100142
Contact: Bixia Tang, MD, PhD 13810211044 bixiatang_med@126.com
Zhongshan Hospital Affiliated to Fudan University	Not yet recruiting
Shanghai, China, 200032
Contact: Xiaoyi Hu, MD, PhD 13917166233 hu.xiaoyi@zs-hospital.sh.cn
Italy
Fondazione del Piemonte per l'Oncologia_Istituto di Candiolo, IRCCS_ Oncologia Medica	Withdrawn
Candiolo, Italy, 10060
A.O. Cannizzaro_UOS Oncologia Medica	Withdrawn
Catania, Italy, 95126
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) UO Oncologia Medica	Withdrawn
Meldola (FC), Italy, 47014
Istituto Europeo di Oncologia_Unità Oncologia Medica Urogenitale e Cervico Facciale	Withdrawn
Milano, Italy, 20141
Istituto Nazionale dei Tumori-Fondazione Pascale- SC Oncologia Medica	Withdrawn
Napoli, Italy, 80131
Azienda Ospedaliero-Universitaria Maggiore della Carità Novara_SC Oncologia Medica	Withdrawn
Novara, Italy, 28100
Istituti Clinici Scientifici Maugeri Spa-SB_ UO Oncologia Medica	Withdrawn
Pavia, Italy, 27100
Azienda Ospedaliero Universitaria Pisana_ UO Oncologia Medica Universitaria	Withdrawn
Pisa, Italy, 56126
Fondazione Policlinico Universitario A. Gemelli, U.O.C. Oncologia Medica	Withdrawn
Roma, Italy, '00168
Korea, Republic of
National Cancer Center - Center For Prostate Cancer	Completed
Goyang-si, Korea, Republic of, 10408
CHA Bundang Medical Center, CHA University	Completed
Seongnam-si, Korea, Republic of, 13496
Severance Hospital, Yonsei University Health System - Medical Oncology	Completed
Seoul, Korea, Republic of, 03722
Asan Medical Center - University of Ulsan College of Medicin	Completed
Seoul, Korea, Republic of, 05505
Samsung Medical Center - Hematology-Oncology	Withdrawn
Seoul, Korea, Republic of, 06351
Poland
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny	Withdrawn
Brzozow, Poland, 36-200
Szpitale Pomorskie Sp. z o.o. Oddział Onkologii i Radioterapii	Withdrawn
Gdynia, Poland, 81-519
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o. Oddział Onkologii Klinicznej z Pododdziałem Dziennym	Completed
Krakow, Poland, 31-826
Clinical Research Center Sp. z o.o., Medic-R Sp. K.	Withdrawn
Poznan, Poland, 60-848
Spain
H.G.U. de Elche	Withdrawn
Elche, Spain, 03203
Hospital Universitario Fundación Jiménez Díaz	Withdrawn
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre	Completed
Madrid, Spain, 28041
H.U. Virgen de la Victoria	Withdrawn
Málaga, Spain, 29010

Sponsors and Collaborators

Xynomic Pharmaceuticals, Inc.

Investigators

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Study Chair:	Pamela Munster, M.D.	University of California, San Francisco
Study Chair:	Rahul Aggarwal, M.D.	University of California, San Francisco

More Information

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Responsible Party:	Xynomic Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT03592472
Other Study ID Numbers:	XYN-602
First Posted:	July 19, 2018 Key Record Dates
Last Update Posted:	May 12, 2021
Last Verified:	May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Xynomic Pharmaceuticals, Inc.:


Renal Cell Carcinoma Progression-free survival Abexinostat	Pazopanib RECIST Cancer therapy

Additional relevant MeSH terms:

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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 Abexinostat Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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