Overview
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).
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
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.