TIVO-1: A Global Phase 3 Trial of Tivozanib in RCC
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is cancer of one or both of the kidneys. The American Cancer Society estimates that there are more than 50,000 new cases of renal cell cancer diagnosed each year. Advanced RCC, which accounts for 80-85% of all malignant kidney tumors, can be very difficult to treat, which is why new treatment options are desperately needed. AVEO is working with leading treatment centers across the country to learn more about tivozanib as a viable treatment option for RCC and other cancers. The company recently achieved its enrollment goal for TIVO-1, its global Phase 3 clinical trial for its oral, triple VEGF receptor inhibitor, tivozanib, in patients with advanced RCC. Initiated in February of this year, TIVO-1 has successfully reached the target enrollment of 500 patients in August 2010.
TIVO-1 Trial Design
TIVO-1 is a global, randomized (1:1), controlled trial evaluating tivozanib compared to sorafenib (Nexavar®). The primary endpoint of the trial is to compare the progression-free survival (PFS) of tivozanib vs. sorafenib. Secondary endpoints include overall survival, objective response rate, duration of response and quality of life. Patients with RCC of clear cell histology that have had a prior nephrectomy and that have not received prior VEGF-targeted therapy are eligible for this trial. Prior to entering the trial, independent, central review of the CT scans was required for all patients to ensure patients met the eligibility criteria regarding measureable disease. During treatment, scans are being obtained every eight weeks, and, again, are centrally reviewed by blinded independent reviewers. Patients who demonstrate disease progression during treatment with sorafenib will have the opportunity to be treated with tivozanib by participating in a separate long-term treatment protocol.
TIVO-1 is being led by Robert Motzer, M.D. from the Memorial Sloan-Kettering Cancer Center and data from this Phase 3 trial are expected to become available in mid-2011.
Tivozanib Phase 2 Trial Showed Positive Safety and Efficacy Data
Prior to launching TIVO-1, AVEO successfully completed a 272-patient Phase 2 clinical trial of tivozanib in patients with advanced RCC. Data from the Phase 2 trial showed that the median PFS achieved by patients with advanced clear cell RCC who had undergone a prior nephrectomy, the patient population also being studied in TIVO-1, was 14.8 months – comparing favorably to historical data from trials testing other currently approved multikinase inhibitors in RCC.
Hypertension, which has been proposed as a biomarker of clinical effect among agents targeting the VEGF receptor tyrosine kinases in RCC, was the most commonly reported treatment-related adverse effect, and was observed in 50% of treated patients. In the study, development of hypertension was directly associated with improved clinical outcomes among patients overall and in the subset of patients with clear cell RCC who had undergone prior nephrectomy. Off-target toxicities commonly associated with other targeted therapies, such as mucositis, fatigue and hand-foot syndrome, were notably low in the tivozanib group, underscoring a favorable tolerability profile and potential for combinability with other therapeutic agents. For more information on the Phase 2 trial, click here.