RecruitingInterventionalPhase 3

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)

NCT ID: NCT03592472Sponsor: Xynomic Pharmaceuticals, Inc.Last updated: 2025-04-13

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.

Arms & interventions

DrugPazopanib
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.
DrugAbexinostat
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.
OtherPlacebo
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.

Outcome measures

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.
Time frame: 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.
Time frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
Overall survival (OS)
Time frame: 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
Time frame: From Day 1 until end of treatment visit (up to approximately 4 years).
Objective response rate (ORR)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (14)

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

Phoenix, Arizona, 85004

Withdrawn

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

Withdrawn

UCSF Helen Diller Family Comphrensive Cancer Center - Hemato

San Francisco, California, 94158

Withdrawn

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, 40202

Completed

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121

Completed

GU Research Network/Urology Cancer Center

Omaha, Nebraska, 68130

Withdrawn

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

Completed

Northwell Health/Monter Cancer Center

Lake Success, New York, 11042

Withdrawn

Mainstreet Physicans Care

Rochester, New York, 14642

Completed

Precision Cancer Research/Dayton Physicians Network - Treatment

Kettering, Ohio, 45409

Withdrawn

Oregon Health and Science University

Portland, Oregon, 97239

Completed

St. Luke's Hospital

Easton, Pennsylvania, 18045

Completed

HOPE Cancer Center of East Texas

Tyler, Texas, 75701

Completed

Medical Oncology Associates, PS (dba Summit Cancer Centers)

Spokane, Washington, 99208

Withdrawn