There was an abstract as ASCO this year giving some background on the stratification done in the trial. 75 % of the participants had already metastases in more than one organ.
Erik
Phase III trial of neovastat in metastatic renal cell carcinoma patients refractory to immunotherapy
Year: 2003
Category: Antiangiogenic or Antimetastatic Agents
Abstract No: 844
Author(s): B. Escudier, P. Venner, R. Buckowski, C. Szczylik, S. Oudard, P. Champagne, C. Hariton, E. Dupont; Institut Gustave Roussy, Villejuif, France; Cross Cancer Institute, Edmonton, AL, Canada; Cleveland Clinic Foundation, Cleveland, OH; CKS WAM, Warsaw, Poland; Hopital Europeen Georges Pompidou, Paris, France; Aeterna Laboratories, Quebec, QC, Canada
Abstract: Cytokines remain the first-line treatment for renal cell carcinoma (RCC). For patients with progressive disease following initial therapy, no standard treatment is available, and new approaches are needed.
Neovastat is a naturally occurring antiangiogenic oral drug with pleiotropic properties. No dose-limiting toxicity was observed in pre-clinical and Phase I/II clinical trials. A phase II trial in RCC patients showed a statistically longer median survival time in patients receiving 240 ml/day vs 60 ml/day (16.3 months vs 7.1 months, p = 0.01).
A prospective, randomized, double-blind, placebo-controlled phase III trial was conducted to determine the efficacy of Neovastat as monotherapy in metastatic RCC patients who had progressed following a first-line of immunotherapy. Eligibility criteria consisted of unresectable metastatic RCC, measurable disease, progressive disease after immunotherapy, and adequate bone marrow, hepatic and renal functions. Patients were stratified according to ECOG performance status (0 vs. 1) and number of metastatic sites (1 vs. >1) and were randomized in a double-blind fashion to Neovastat (120 ml B.I.D.) or placebo (ratio 1:1).
The primary endpoint was median survival time and statistical hypothesis was improvement from 8 to 12+ months. Time to progression, one-year survival rate, quality of life, overall tumor response rate and duration of response were secondary endpoints.
From May 2000 to January 2002, 302 patients were recruited in 46 centers (Argentina, Canada, Europe and USA). Median age was 61 years (25 to 81) with 75% (222) males and 25% (80) females. Fifty-two percent (52%) of the patients had ECOG 0. Seventy-five (75) patients had metastases restricted to one site. 227 patients had more than one metastatic site (lung, 70%; liver, 25%; bone, 29%). The safety profile of Neovastat appears acceptable and demonstrated no severe toxicity in either arm according to an independent Data Safety Monitoring Board review. Conclusion: This study will provide key data on survival of patients with refractory RCC and will provide insights on the clinical activity of Neovastat. Mature data will be presented at the meeting.
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