A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (TIVO-1)
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|ClinicalTrials.gov Identifier: NCT01030783|
Recruitment Status : Completed
First Posted : December 11, 2009
Results First Posted : October 28, 2019
Last Update Posted : October 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Renal Cell Carcinoma||Drug: tivozanib (AV-951) Drug: Sorafenib||Phase 3|
This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.
Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib and stratified by geographic region (North America/Western Europe, Central/Eastern Europe, or rest of the world); number of prior treatments (0 or 1); and number of metastatic sites/organs involved (1 or ≥ 2).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||517 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (TIVO-1)|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||July 2012|
|Actual Study Completion Date :||June 2013|
|Experimental: tivozanib (AV-951)||
Drug: tivozanib (AV-951)
Tivozanib: 1.5 mg orally once daily. Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.
|Active Comparator: sorafenib||
Sorafenib: 400 mg orally twice daily. Subjects will receive 400 mg (2 x 200 mg tablets) sorafenib twice daily continuously, beginning on Day 1. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.
- Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib [ 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) 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 1.0 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) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [ 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. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive. Subjects lacking data beyond randomization will have their survival times censored on the date of randomization.
- Objective Response Rate (ORR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [ 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 1.0).
- Duration of Response (DR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib [ Time Frame: Assessed every 8 weeks from date of randomization until date of progression ]Duration of response (DR) is defined as the time from the first documentation of objective tumor response to the first documentation of tumor progression per RECIST 1.0 or to death due to any cause.
- Safety and Tolerability of Tivozanib and Sorafenib [ Time Frame: From start of treatment therapy to completion of treatment therapy, an average of 11 months ]Dose reductions and interruptions were allowed for subjects taking tivozanib or sorafenib. Any modification of study drug administration, and the reason for such action, was clearly noted on the subject's eCRF.
- To Compare Kidney-specific Symptoms and Health Outcome Measurements in Subjects Randomized to Treatment With Tivozanib or Sorafenib [ Time Frame: At Day 1 of each 28 day cycle throughout the course of the study, for an average of 11 months per subject ]The Disease Related Symptom Scale of the Functional Assessment of Cancer Therapy - Advanced Kidney Cancer Symptom Index (FKSI-DRS) measured kidney specific symptoms on a 0-36 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. The Functional Assessment of Cancer Therapy-General (FACT-G) measured general wellbeing scored on a 0-108 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. The European Quality of Life-5 Dimensions (EQ-5D) measured patient health related quality of life scored on a 0-1 scale, with 0 being worse health state and 1 being perfect health state. The European Quality of Life-5 Dimensions Visual Analog Scales (EQ-5D VAS) measured patient health related quality of life on a visual analog scale from 0 to 100, with 0 being the worst and 100 being the best. These scales were self-administered by patients at the start of the visit.
- Pharmacokinetics (Serum Concentrations) of Tivozanib [ Time Frame: Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28 ]Samples for tivozanib serum concentrations will be collected at the following time points: Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28. The serum concentrations of tivozanib were tabulated for individual subjects and summarized by nominal time using standard descriptive statistics (concentrations presented in ng/mL).
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): NCT01030783
|Principal Investigator:||Robert J. Motzer, MD||Memorial Sloan Kettering Cancer Center|