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)
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).
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Xynomic Pharmaceuticals, Inc. |
United States, China, Italy, Korea, Republic of, Poland, Spain,
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). |
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