Clinical trial NCT03592472: A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Renal Cell Carcinoma
Keywords: Renal Cell Carcinoma
Progression-free survival
Abexinostat
Pazopanib
RECIST
Cancer therapy
Lead sponsor: Xynomic Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-19
Enrollment: 413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
Secondary outcomes:
measure: PFS by investigator assessment according to RECIST version 1.1.
timeFrame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
measure: Overall survival (OS)
timeFrame: 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).
measure: Adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5
timeFrame: From Day 1 until end of treatment visit (up to approximately 4 years).
measure: Objective response rate (ORR)
timeFrame: 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).
measure: Duration of response (DOR)
timeFrame: 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).
measure: ORR by RECIST version 1.1 in cross-over patient population
timeFrame: 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).
measure: DOR by RECIST version 1.1 in cross-over patient population
timeFrame: 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).
measure: Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) scores
timeFrame: 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).
measure: Mean change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT-F) scores
timeFrame: 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).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: University Of UA Cancer Center(UACC)/DH-SJHMC
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comphrensive Cancer Center - Hemato
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute, Norton Healthcare Pavilion
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Omaha
country: United States
facility: GU Research Network/Urology Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Lake Success
country: United States
facility: Northwell Health/Monter Cancer Center
state: New York
city: Rochester
country: United States
facility: Mainstreet Physicans Care
state: New York
city: Kettering
country: United States
facility: Precision Cancer Research/Dayton Physicians Network - Treatment
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Easton
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Tyler
country: United States
facility: HOPE Cancer Center of East Texas
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, PS (dba Summit Cancer Centers)
state: Washington
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia_Istituto di Candiolo, IRCCS_ Oncologia Medica
city: Catania
country: Italy
facility: A.O. Cannizzaro_UOS Oncologia Medica
city: Meldola (FC)
country: Italy
facility: IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) UO Oncologia Medica
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia_Unità Oncologia Medica Urogenitale e Cervico Facciale
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori-Fondazione Pascale- SC Oncologia Medica
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore della Carità Novara_SC Oncologia Medica
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri Spa-SB_ UO Oncologia Medica
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana_ UO Oncologia Medica Universitaria
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli, U.O.C. Oncologia Medica
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center - Center For Prostate Cancer
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System - Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - University of Ulsan College of Medicin
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - Hematology-Oncology
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o. Oddział Onkologii i Radioterapii
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o. Oddział Onkologii Klinicznej z Pododdziałem Dziennym
city: Poznan
country: Poland
facility: Clinical Research Center Sp. z o.o., Medic-R Sp. K.
city: Elche
country: Spain
facility: H.G.U. de Elche
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: H.U. Virgen de la Victoria
Study officials:
affiliation: University of California, San Francisco
name: Pamela Munster, M.D.
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Rahul Aggarwal, M.D.
role: STUDY_CHAIR
References: