TriangleNCT02627963 · CITED IN SOURCE DOCUMENTS
A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2023-07-18
This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced renal cell carcinoma (RCC). Participants will be randomized (1:1) to treatment with tivozanib or sorafenib. Participants 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 participants 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) analyses are also included in study.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 18 years or older * Participants 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 (participants 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. Participants 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants randomized to this arm will receive the study drug, tivozanib hydrochloride.
- intervention Names
- Drug: Tivozanib hydrochloride
- label
- Tivozanib hydrochloride
- type
- EXPERIMENTAL
- description
- Participants randomized to this arm will receive the comparator drug, sorafenib.
- intervention Names
- Drug: Sorafenib
- label
- Sorafenib
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Tivozanib hydrochloride
- description
- Tivozanib hydrochloride
- name
- Tivozanib hydrochloride
- type
- DRUG
- arm Group Labels
- Sorafenib
- description
- Sorafenib
- name
- Sorafenib
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 350
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- The 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.
- measure
- 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 (up to approximately 5 years)
- secondary Outcomes
- description
- The OS is defined as the time from the date of randomization to date of death due to any cause.
- measure
- Overall Survival (OS)
- time Frame
- Date of randomization to date of death (up to approximately 5 years)
- description
- The ORR is defined as the percentage of participants who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).
- measure
- Objective Response Rate (ORR)
- time Frame
- Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)
- description
- The 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.
- measure
- Duration of Response (DOR)
- time Frame
- Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)
Full study description
- brief Summary
- This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced renal cell carcinoma (RCC). Participants will be randomized (1:1) to treatment with tivozanib or sorafenib. Participants 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 participants 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) analyses are also included in study.
Source references
- references
- citation
- Beckermann KE, Asnis-Alibozek AG, Atkins MB, Escudier B, Hutson TE, Kasturi V, McDermott DF, Pal SK, Porta C, Rini BI, Verzoni E. Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial. Oncologist. 2024 Mar 4;29(3):254-262. doi: 10.1093/oncolo/oyad348.
- pmid
- 38262444
- type
- DERIVED
- citation
- Meza L, McDermott DF, Escudier B, Hutson TE, Porta C, Verzoni E, Atkins MB, Kasturi V, Pal SK, Rini B. Tivozanib in Patients with Advanced Renal Cell Carcinoma Previously Treated With Axitinib: Subgroup Analysis from TIVO-3. Oncologist. 2023 Mar 17;28(3):e167-e170. doi: 10.1093/oncolo/oyac255.
- pmid
- 36576430
- type
- DERIVED
- citation
- Szarek M, Needle MN, Rini BI, Pal SK, McDermott DF, Atkins MB, Hutson TE, Escudier BJ. Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study. Clin Genitourin Cancer. 2021 Oct;19(5):468.e1-468.e5. doi: 10.1016/j.clgc.2021.03.018. Epub 2021 Apr 3.
- pmid
- 33980467
- type
- DERIVED
- citation
- 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.
- pmid
- 31810797
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice