A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
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| ClinicalTrials.gov Identifier: NCT02627963 |
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Recruitment Status :
Completed
First Posted : December 11, 2015
Results First Posted : February 20, 2020
Last Update Posted : July 18, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Renal Cell | Drug: Tivozanib hydrochloride Drug: Sorafenib | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 350 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 24, 2016 |
| Actual Primary Completion Date : | October 4, 2018 |
| Actual Study Completion Date : | June 21, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Tivozanib hydrochloride
Participants randomized to this arm will receive the study drug, tivozanib hydrochloride.
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Drug: Tivozanib hydrochloride
Tivozanib hydrochloride |
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Active Comparator: Sorafenib
Participants randomized to this arm will receive the comparator drug, sorafenib.
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Drug: Sorafenib
Sorafenib |
- 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) ]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.
- Overall Survival (OS) [ Time Frame: Date of randomization to date of death (up to approximately 5 years) ]The 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 (up to approximately 5 years) ]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).
- Duration of Response (DOR) [ Time Frame: Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years) ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02627963
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Documents provided by AVEO Pharmaceuticals, Inc.:
| Responsible Party: | AVEO Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT02627963 |
| Other Study ID Numbers: |
AV-951-15-303 |
| First Posted: | December 11, 2015 Key Record Dates |
| Results First Posted: | February 20, 2020 |
| Last Update Posted: | July 18, 2023 |
| Last Verified: | June 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
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Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases |
Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Kidney Diseases Urologic Diseases Male Urogenital Diseases Sorafenib Tivozanib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |