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

Renal Cell Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03592472
• Other study ID #: XYN-602
• Status: Recruiting
• Phase: Phase 3
• Start date: July 17, 2018
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Xynomic Pharmaceuticals, Inc.
• Contact: Sophia Paspal, Ph.D.
• Phone: 6104055974
• Email: sophia.paspal[@]xynomicpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 413
• Est. completion date: June 30, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

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.
• 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:
• 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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Zhongshan Hospital Affiliated to Fudan University	Shanghai
Italy	Fondazione del Piemonte per l'Oncologia_Istituto di Candiolo, IRCCS_ Oncologia Medica	Candiolo
Italy	A.O. Cannizzaro_UOS Oncologia Medica	Catania
Italy	IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) UO Oncologia Medica	Meldola (FC)
Italy	Istituto Europeo di Oncologia_Unità Oncologia Medica Urogenitale e Cervico Facciale	Milano
Italy	Istituto Nazionale dei Tumori-Fondazione Pascale- SC Oncologia Medica	Napoli
Italy	Azienda Ospedaliero-Universitaria Maggiore della Carità Novara_SC Oncologia Medica	Novara
Italy	Istituti Clinici Scientifici Maugeri Spa-SB_ UO Oncologia Medica	Pavia
Italy	Azienda Ospedaliero Universitaria Pisana_ UO Oncologia Medica Universitaria	Pisa
Italy	Fondazione Policlinico Universitario A. Gemelli, U.O.C. Oncologia Medica	Roma
Korea, Republic of	National Cancer Center - Center For Prostate Cancer	Goyang-si
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si
Korea, Republic of	Asan Medical Center - University of Ulsan College of Medicin	Seoul
Korea, Republic of	Samsung Medical Center - Hematology-Oncology	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System - Medical Oncology	Seoul
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny	Brzozow
Poland	Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii	Gdynia
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o. Oddzial Onkologii Klinicznej z Pododdzialem Dziennym	Krakow
Poland	Clinical Research Center Sp. z o.o., Medic-R Sp. K.	Poznan
Spain	H.G.U. de Elche	Elche
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	H.U. Virgen de la Victoria	Málaga
United States	St. Luke's Hospital	Easton	Pennsylvania
United States	Precision Cancer Research/Dayton Physicians Network - Treatment	Kettering	Ohio
United States	Northwell Health/Monter Cancer Center	Lake Success	New York
United States	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	GU Research Network/Urology Cancer Center	Omaha	Nebraska
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	University Of UA Cancer Center(UACC)/DH-SJHMC	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Mainstreet Physicans Care	Rochester	New York
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	UCSF Helen Diller Family Comphrensive Cancer Center - Hemato	San Francisco	California
United States	Medical Oncology Associates, PS (dba Summit Cancer Centers)	Spokane	Washington
United States	HOPE Cancer Center of East Texas	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Xynomic Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  China,  Italy,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
Secondary	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.	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).
Secondary	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.	From Day 1 until end of treatment visit (up to approximately 4 years).
Secondary	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.	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).
Secondary	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.	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).
Secondary	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.	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).
Secondary	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.	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).
Secondary	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).	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).
Secondary	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).	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).