Advanced Renal Cell Carcinoma MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tivozanib
Product Code: AV-951
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tivozanib hydrochloride monohydrate
CAS Number: 682745-41-1
Current Sponsor code: AV-951
Other des
Sponsors
AVEO PHARMACEUTICALS, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. = 18-years of age. 2. 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. 3. Subjects must have recovered from the AEs of prior therapy or returned to baseline. Controlled AEs such as hypothyroidism or hypertension are permitted. 4. 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). 5. Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy = 3 months. 8. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment. 9. Ability to give written informed consent and comply with protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: 1. Prior treatment with sorafenib or tivozanib. 2. More than 3 prior regimens for metastatic RCC. 3. 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). 4. Significant cardiovascular disease 5. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug 6. Significant bleeding disorders 7. Currently active second primary malignancy 8. Pregnant or lactating females. 9. Participation in another interventional protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of subjects with refractory advanced renal cell carcinoma (RCC) randomized to treatment with tivozanib hydrochloride (tivozanib) or sorafenib as assessed by blinded independent radiological review (IRR) of computerized tomography (CT) or magnetic resonance imaging (MRI).;Secondary Objective: To compare the overall survival (OS) of subjects randomized to treatment with tivozanib or sorafenib. To compare objective response rate (ORR) and duration of response (DoR) of subjects randomized to treatment with tivozanib or sorafenib. To compare the safety and tolerability of tivozanib and sorafenib.;Primary end point(s): • To compare the PFS of subjects dosed with tivozanib with those subjects dosed with sorafenib. ;Timepoint(s) of evaluation of this end point: Analysis will be done at the time of the final PFS analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To compare the OS between the 2 treatment arms by using stratified Log-rank test and the stratification factors included in the primary analysis. • To analyze OS, ORR, and DoR using the investigator and independent radiological review assessments (starting with version 5 of the protocol, all clinical response decisions will be based on local radiological review). ;Timepoint(s) of evaluation of this end point: The first interim OS analysis (conducted in October 2018) occurred at the Primary PFS analysis with 183 OS events (70% information fraction) observed with alpha spending of 0.007. The second interim analysis occurred when all subjects had been onstudy for at least two years (August 15, 2019), with 86% information fraction observed with 0.014 cumulative alpha spent at this time. The final OS analysis will occur on May 1, 2020 based on an estimate of approximately 4 OS events occurring per month (or approximately 263 OS events at that time). | — |
Countries
Australia, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactAVEO pharma limited
AVEO Pharma Ltd.
Outcome results
None listed