A phase II trial of intra-patient dose escalated-sorafenib in patients (pts) with metastatic renal cell cancer (MRCC)

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Abstract
5122 Background: An earlier phase II study (J Clin Oncol. Vol 25, No. 18S, 2007: Abstract 5026), we were able to show that pts who were able to tolerate doses higher than the FDA-approved dose have significantly improved clinical outcomes, including remission, tumor shrinkage, growth arrest and will have lesser side effects over time. We have expanded the phase II study to determine if an increase in dose will result in higher AUC and Cmax level. Response rate, progression free survival (PFS) and overall survival (OS) was assessed. Methods: Pts had a confirmed component of clear cell RCC, progressive measurable metastatic disease, adequate organ/marrow function, and no more than 1 prior therapy. The initial dose of sorafenib was 400 mg PO, BID, daily days 1 to 28. Dose escalation was defined as; on day 29 through day 56, an increase to 600 mg BID and on day 57 throughout as tolerated 800 mg BID daily. Dose modifications were performed for toxicity per the National Cancer Institute Common Toxicity Criteria Version 3.0. Pts were evaluated every 2 cycles (8 weeks) using RECIST. PFS and OS were determined from entry into the study. Blood and urine samples are obtained on days 28, 56, and 84. Results: Twenty-two pts were enrolled to date, 19 are evaluable for a response and toxicity, and 3 for toxicity only. One pt had a complete response (CR), 5 pts partial response (PR) and 7 pts stable disease (SD) for 3 months or more. One pt had progressive disease and it is still too early to assess 5 pts. Most common treatment related adverse events; hand/foot syndrome, skin rash, diarrhea, alopecia, fatigue and hypertension. Noted laboratory abnormalities; hypophosphatemia. Conclusions: 14/14 pts were escalated to 1,600 mg per day. Dose escalated sorafenib has promising anti-tumor activity in pts with MRCC as demonstrated by a 32% CR/PR rate and is further suggested by a prolonged PFS ≥3 months for an additional 50% of pts. Intra-patient dose escalation data in association with anti-tumor activity and toxicity in correlation with pharmacokinetic studies will be presented, in addition to an update of the ASCO 2007 data.

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