A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced RCC

• ClinicalTrials.gov Identifier: NCT02627963
• Recruitment Status: Active, not recruiting
• First Posted: December 11, 2015
• Results First Posted: February 20, 2020
• Last Update Posted: February 2, 2021
• Sponsor: AVEO Pharmaceuticals, Inc.
• Information provided by (Responsible Party): AVEO Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: December 9, 2015
• First Posted Date: December 11, 2015
• Results First Submitted Date: January 16, 2020
• Results First Posted Date: February 20, 2020
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: April 2016
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2020)

Progression-free Survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks. ]

Progression-Free Survival (PFS), as assessed by a blinded independent radiological review (IRR), is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.1 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

• Original Primary Outcome Measures (submitted: December 10, 2015): Progression-free Survival (PFS) [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: February 10, 2020)

• Overall Survival (OS) [ Time Frame: Date of randomization to date of death ]
  Overall survival (OS) is defined as the time from the date of randomization to date of death due to any cause.
• Objective Response Rate (ORR) [ Time Frame: Every 8 weeks from date of randomization until disease progression ]
  Objective response rate (ORR) is defined as the percentage of subjects who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).
• Duration of Response (DOR) [ Time Frame: Assessed every 8 weeks from date of randomization until date of progression ]
  Duration of response (DOR) is defined as the time from the first documentation of objective tumor response to the first documentation of tumor progression per RECIST 1.1 or to death due to any cause.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced RCC
• Official Title: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma

Brief Summary

This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC).

Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib.

Subjects will be stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category (favorable; intermediate; poor) and prior therapy (two prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI); a prior checkpoint inhibitor [programmed cell death -1 protein (PD-1) or PD-1 ligand (PD1-L) inhibitor] plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent).

All subjects will be evaluated for progression free survival, overall survival, objective response rate, and the duration of response as well as safety and tolerability.

Pharmacokinetic (PK) analysis are also included in study.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Renal Cell

Intervention

• Drug: tivozanib hydrochloride
  tivozanib hydrochloride
• Drug: Sorafenib
  Sorafenib

Study Arms

• Experimental: Tivozanib hydrochloride
  Patients randomized to this arm will receive the study drug, tivozanib hydrochloride.
  Intervention: Drug: tivozanib hydrochloride
• Active Comparator: Sorafenib
  Patients randomized to this arm will receive the comparator drug, sorafenib.
  Intervention: Drug: Sorafenib

• Publications *: Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95-104. doi: 10.1016/S1470-2045(19)30735-1. Epub 2019 Dec 3.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 5, 2019): 350
• Original Estimated Enrollment (submitted: December 10, 2015): 322
• Estimated Study Completion Date: June 2021
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 18 years or older
• Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib.
• Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, and unclassified RCC are excluded).
• Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.

Exclusion Criteria:

• Prior treatment with sorafenib or tivozanib.
• More than 3 prior regimens for metastatic RCC.
• Known central nervous system (CNS) metastases other than stable, treated brain metastases. Subjects with previously treated brain metastasis will be allowed if the brain metastasis has been stable by neuroimaging without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
• Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders.
• Significant serum chemistry abnormalities
• Significant cardiovascular disease, including: Active clinically symptomatic left ventricular failure,uncontrolled hypertension, myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring anti-arrhythmic medications.
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
• Currently active second primary malignancy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02627963
• Other Study ID Numbers: AV-951-15-303
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: AVEO Pharmaceuticals, Inc.
• Study Sponsor: AVEO Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial; AVEO Pharmaceuticals, Inc.

• PRS Account: AVEO Pharmaceuticals, Inc.
• Verification Date: January 2021