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

Официальное название

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)

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Другое 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.

Первичные конечные точки

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

Вторичные конечные точки (9)

• PFS by investigator assessment according to RECIST version 1.1. [Срок оценки: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).]
• Overall survival (OS) [Срок оценки: 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 [Срок оценки: From Day 1 until end of treatment visit (up to approximately 4 years).]
• Objective response rate (ORR) [Срок оценки: 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) [Срок оценки: 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).]
• ORR by RECIST version 1.1 in cross-over patient population [Срок оценки: 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 by RECIST version 1.1 in cross-over patient population [Срок оценки: 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).]
• Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) scores [Срок оценки: 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).]
• Mean change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT-F) scores [Срок оценки: 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).]

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 14 центров

• University Of UA Cancer Center(UACC)/DH-SJHMC — Phoenix
• University of California Davis Comprehensive Cancer Center — Sacramento
• UCSF Helen Diller Family Comphrensive Cancer Center - Hemato — San Francisco
• Norton Cancer Institute, Norton Healthcare Pavilion — Louisville
• Ochsner Clinic Foundation — New Orleans
• GU Research Network/Urology Cancer Center — Omaha
• Nebraska Cancer Specialists — Omaha
• Northwell Health/Monter Cancer Center — Lake Success
• … и ещё 6 центров

Италия · 9 центров

• Fondazione del Piemonte per l'Oncologia_Istituto di Candiolo, IRCCS_ Oncologia Medica — Candiolo
• A.O. Cannizzaro_UOS Oncologia Medica — Catania
• IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) UO Oncologi — Meldola (FC)
• Istituto Europeo di Oncologia_Unità Oncologia Medica Urogenitale e Cervico Facciale — Milan
• Istituto Nazionale dei Tumori-Fondazione Pascale- SC Oncologia Medica — Naples
• Azienda Ospedaliero-Universitaria Maggiore della Carità Novara_SC Oncologia Medica — Novara
• Istituti Clinici Scientifici Maugeri Spa-SB_ UO Oncologia Medica — Pavia
• Azienda Ospedaliero Universitaria Pisana_ UO Oncologia Medica Universitaria — Pisa
• … и ещё 1 центр

South Korea · 5 центров

• National Cancer Center - Center For Prostate Cancer — Goyang-si
• CHA Bundang Medical Center, CHA University — Seongnam-si
• Severance Hospital, Yonsei University Health System - Medical Oncology — Seoul
• Asan Medical Center - University of Ulsan College of Medicin — Seoul
• Samsung Medical Center - Hematology-Oncology — Seoul

Польша · 4 центра

• Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny — Brzozów
• Szpitale Pomorskie Sp. z o.o. Oddział Onkologii i Radioterapii — Gdynia
• Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o. Oddział Onkologii Klin — Krakow
• Clinical Research Center Sp. z o.o., Medic-R Sp. K. — Poznan

Испания · 4 центра

• H.G.U. de Elche — Elche
• Hospital Universitario Fundación Jiménez Díaz — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• H.U. Virgen de la Victoria — Málaga

Китай · 2 центра

• Beijing Cancer Hospital — Пекин
• Zhongshan Hospital Affiliated to Fudan University — Шанхай

Идентификаторы

NCT: NCT03592472 · XYN-602

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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