Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4530
© 2006 American Society of Clinical Oncology

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Abstract

A phase II trial of RAD001 in patients (Pts) with metastatic renal cell carcinoma (MRCC)

Methodist Hospital Research Institute, Houston, TX

4530

Background: RAD001 an oral serine-threonine kinase inhibitor of mTOR, blocks progression from the GI to the S phase of the cell cycle by a mechanism of action that is unique for an anticancer drug. Mechanistically, it is thought that RAD001 may play a role in VEGF inhibition. Main endpoints were to evaluate: time to progression (TTP), response rate, toxicity and to assess changes in metabolic imaging utilizing CT-PET. Methods: Eligibility included: progressive measurable MRCC, adequate organ/marrow function, zubrod performance status (ZPS) 2, no more than 1 prior therapy, and no active CNS involvement. RAD001 is given orally at a dose of 10mg daily without an interruption (28-day cycle), with dose modifications for toxicity. Re-evaluation was assessed every 3 cycles (12 weeks). RECIST criteria is utilized to determine response rate. TTP is determined from entry into the study. Results: 25 pts have been enrolled as of this review. 19 male/6 female, range 43–80 (median 60) years. All pts had predominant clear cell elements with progressive MRCC. 17 pts received prior immunotherapy, targeted agents, or chemotherapy. 22 pts had a ZPS of 0, 2/1 and 1/2. Sites of disease included: lung, nodal, bone, adrenal, kidney and liver. 7 pts had 1 metastatic site, 10 pts/2 metastatic sites and 8 pts/3 or more metastatic sites. 22 pts continue to receive RAD001 therapy. 7 pts had partial responses, 11 pts were stable for 3+ months, (5 pts/6+ months). 4 pts too early. Median duration of therapy is 7+ months (range 1+ to 9+). Treatment related adverse events to date include: mucositis, skin rash, pneumonitis, hypophosphatemia, hyperglycemia, thrombocytopenia, anemia and elevated LFTs. Conclusion: RAD001 has promising anti-tumor activity in pts with MRCC as demonstrated by a 33% partial response rate. Anti-tumor activity was further suggested by prolonged TTP 3 months for 86% of pts. The tumor effect was also demonstrated as a second line therapy. Independent radiology review is planned. Anti-tumor activity, toxicity and metabolic imaging correlation will be presented.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Council of Healthcare Advisors, ImClone Bayer, Onyx, Chiron, Ingenix, Pfizer, sanofi-aventis

Abstract presentation from the 2006 ASCO Annual Meeting