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

NCT03592472 | Recruiting Phase 3 FDA Drug

• 1 other identifier: XYN-602
• Study Type: interventional
• Target: 413
• Locations: 6 countries
• Sites: 38

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).

Conditions

Renal Cell Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomization date to date of first documentation of progression OR death (up to approximately 4 years).

Secondary Outcomes (9)

• PFS by investigator assessment according to RECIST version 1.1.

  From randomization date to date of first documentation of progression OR death (up to approximately 4 years).

• Overall survival (OS)

  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

  From Day 1 until end of treatment visit (up to approximately 4 years).

• Objective response rate (ORR)

  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)

  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).

Study Arms (2)

Pazopanib plus abexinostat

EXPERIMENTAL

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; Drug: Abexinostat

Pazopanib plus placebo

PLACEBO COMPARATOR

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: Placebo

Interventions

Pazopanib DRUG

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.

Also known as: Votrient®

Pazopanib plus abexinostat; Pazopanib plus placebo

Abexinostat DRUG

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.

Also known as: PCI-24781

Pazopanib plus abexinostat

Placebo OTHER

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.

Pazopanib plus placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xynomic Pharmaceuticals, Inc.: lead

Study Sites (38)

University Of UA Cancer Center(UACC)/DH-SJHMC

Phoenix, Arizona, 85004, United States

WITHDRAWN

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

WITHDRAWN

UCSF Helen Diller Family Comphrensive Cancer Center - Hemato

San Francisco, California, 94158, United States

WITHDRAWN

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, 40202, United States

COMPLETED

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

COMPLETED

GU Research Network/Urology Cancer Center

Omaha, Nebraska, 68130, United States

WITHDRAWN

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

COMPLETED

Northwell Health/Monter Cancer Center

Lake Success, New York, 11042, United States

WITHDRAWN

Mainstreet Physicans Care

Rochester, New York, 14642, United States

COMPLETED

Precision Cancer Research/Dayton Physicians Network - Treatment

Kettering, Ohio, 45409, United States

WITHDRAWN

Oregon Health and Science University

Portland, Oregon, 97239, United States

COMPLETED

St. Luke's Hospital

Easton, Pennsylvania, 18045, United States

COMPLETED

HOPE Cancer Center of East Texas

Tyler, Texas, 75701, United States

COMPLETED

Medical Oncology Associates, PS (dba Summit Cancer Centers)

Spokane, Washington, 99208, United States

WITHDRAWN

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

Zhongshan Hospital Affiliated to Fudan University

Shanghai, 200032, China

NOT YET RECRUITING

Fondazione del Piemonte per l'Oncologia_Istituto di Candiolo, IRCCS_ Oncologia Medica

Candiolo, 10060, Italy

WITHDRAWN

A.O. Cannizzaro_UOS Oncologia Medica

Catania, 95126, Italy

WITHDRAWN

IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) UO Oncologia Medica

Meldola (FC), 47014, Italy

WITHDRAWN

Istituto Europeo di Oncologia_Unità Oncologia Medica Urogenitale e Cervico Facciale

Milan, 20141, Italy

WITHDRAWN

Istituto Nazionale dei Tumori-Fondazione Pascale- SC Oncologia Medica

Napoli, 80131, Italy

WITHDRAWN

Azienda Ospedaliero-Universitaria Maggiore della Carità Novara_SC Oncologia Medica

Novara, 28100, Italy

WITHDRAWN

Istituti Clinici Scientifici Maugeri Spa-SB_ UO Oncologia Medica

Pavia, 27100, Italy

WITHDRAWN

Azienda Ospedaliero Universitaria Pisana_ UO Oncologia Medica Universitaria

Pisa, 56126, Italy

WITHDRAWN

Fondazione Policlinico Universitario A. Gemelli, U.O.C. Oncologia Medica

Roma, '00168, Italy

WITHDRAWN

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny

Brzozów, 36-200, Poland

WITHDRAWN

Szpitale Pomorskie Sp. z o.o. Oddział Onkologii i Radioterapii

Gdynia, 81-519, Poland

WITHDRAWN

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o. Oddział Onkologii Klinicznej z Pododdziałem Dziennym

Krakow, 31-826, Poland

COMPLETED

Clinical Research Center Sp. z o.o., Medic-R Sp. K.

Poznan, 60-848, Poland

WITHDRAWN

National Cancer Center - Center For Prostate Cancer

Goyang-si, 10408, South Korea

COMPLETED

CHA Bundang Medical Center, CHA University

Seongnam-si, 13496, South Korea

COMPLETED

Severance Hospital, Yonsei University Health System - Medical Oncology

Seoul, 03722, South Korea

COMPLETED

Asan Medical Center - University of Ulsan College of Medicin

Seoul, 05505, South Korea

COMPLETED

Samsung Medical Center - Hematology-Oncology

Seoul, 06351, South Korea

WITHDRAWN

H.G.U. de Elche

Elche, 03203, Spain

WITHDRAWN

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

WITHDRAWN

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

COMPLETED

H.U. Virgen de la Victoria

Málaga, 29010, Spain

WITHDRAWN

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pazopanib; abexinostat

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Pamela Munster, M.D.

  University of California, San Francisco

  STUDY CHAIR

• Rahul Aggarwal, M.D.

  University of California, San Francisco

  STUDY CHAIR

Central Study Contacts

Sophia Paspal, Ph.D.

CONTACT

6104055974; sophia.paspal@xynomicpharma.com

Rahul Aggarwal, M.D.

CONTACT

rahul.aggarwal@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study. The sponsor, investigators, study coordinators, and the patients will be blinded to the study drug (abexinostat/placebo).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2018
• First Posted: July 19, 2018
• Study Start: July 17, 2018
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); CN (2); IT (9); PL (4); KR (5); ES (4)