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

Xynomic Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Renal Cell Carcinoma

Treatments: Other: Placebo; Drug: Abexinostat; Drug: Pazopanib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03592472

XYN-602

Details and patient eligibility

About

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).

Full 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.

Enrollment: 413 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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413 participants in 2 patient groups, including a placebo group

Pazopanib plus abexinostat

Experimental group

Description:

Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.

Treatment:

Drug: Pazopanib

Drug: Abexinostat

Pazopanib plus placebo

Placebo Comparator group

Description:

Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo 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. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.

Treatment:

Drug: Pazopanib

Other: Placebo