A phase II study of PTK787 in metastatic melanoma patients.

9048 Background: Melanoma overexpresses vascular endothelial growth factor receptor (VEGFR). Preclinically, inhibition of melanoma growth can be controlled with a variety of anti-VEGF strategies. PTK787 (Bayer Schering Pharma) is an oral tyrosine kinase inhibitor of VEGFR-1 and -2. METHODS: A phase II study of PTK787 was undertaken to evaluate the efficacy and safety of PTK 787 in patients (pts) with metastatic cutaneous melanoma. Primary endpoint was disease control rate. Using Fleming's single stage design, 34 patients were required. Eligibility criteria included measurable disease by RECIST and 1 prior treatment for metastatic melanoma was allowed. Patients with at least 1 liver metastasis of >4cm were offered additional dce-MRI scans prior to, 1 week and 4 weeks after starting treatment. Blood to measure soluble markers of angiogenesis was taken prior to and every 4 weeks during treatment. Treatment was escalated weekly depending on tolerance, from 250 mg twice daily, to 500 mg twice daily, to 500 mg morning, 750 mg evening as a maximum daily dose, which was continued until progression or unacceptable toxicity. RESULTS: 34 pts were enrolled across 2 UK sites. Median age was 58 years, 60 % male, 28% had received 1 prior treatment. Data on 29 patients receiving at least 1 cycle of treatment has been analysed so far. 44% of pts achieved the maximum daily dose for the duration of their treatment, 19% required a dose reduction due to drug-related toxicity, and 37% never achieved the maximum dose due to drug-related toxicity. Grade 3 adverse events were hypertension (2 pts), vomiting (1 pt), diarrhoea (1 pt), disorientation (1pt), fatigue (1pt), neutropenia (1pt). The majority of dose modifications were for a combination of grade 2 toxicities, most commonly proteinuria (41%), nausea and vomiting (34%), fatigue (24%) and dizziness (14%). At the time of analysis, 21 pts were assessable for response. The disease control rate was 43% (1 PR, 8 stable disease, 12 progression). All pts achieving disease control (PR and stable) remain alive, with survival times of 2.6 - 11.6 months to date. CONCLUSIONS: The final clinical outcome data as well as radiological and pharmacological studies of angiogenic markers will be presented. No significant financial relationships to disclose.