A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603.

4515 Background: S is an oral broad-spectrum tyrosine kinase (TK) inhibitor with potential utility in PAC given the perturbation of multiple signaling pathways and stromal alterations noted in PAC. CALGB conducted an NCI-sponsored phase II study of S in patients (pts) with previously-treated PAC. METHODS: Eligibility included: PAC previously treated with front-line gemcitabine (gem) therapy, or progression of disease (PD) during or within 3-months of completion of adjuvant therapy, or newly metastatic disease following therapy for locally advanced PAC; performance status 0-2; measurable disease by RECIST; no prior anti-VEGF therapy; no evidence of duodenal invasion on CT. S was dosed at 50 mg daily for 28 days followed by 14 days of rest (1 cycle). Re-staging was performed after each of the first 4 cycles of therapy. STUDY DESIGN: Single-arm, multi-center cooperative group, 3-stage design, with response criteria of at least stable disease (SD) in 1/19, 2/39, for expansion. Planned accrual was 64. Primary endpoint: Response rate (RECIST). Secondary endpoints: Duration of response, toxicity, PFS, and survival. RESULTS: From 11/06 to 11/07, 77 pts were accrued with the criteria met for full accrual (1 withdrew consent). Pt characteristics were: male 54%, female 46%, age: median 65 yrs, range 42- 87, and PS 0/1/2 45%/48%/7%. Prior therapy included: gem 61%, gem-based combination 37%, TK inhibitor 14%, radiation therapy 14%. Sites of disease were: liver 84%, lung 30%, other 19%. As of 12/07, 52 pts are evaluable for response. Response criteria for continuation were met at the two interim analyses. SD occurred in 7 pts [13%, 95% CI (3.6%, 22%)] and PD in 29 (56%). Number of cycles received was: 1- 86%; 2- 12%, 3- 2%. Dose modification was needed in 21%. Median PFS was 41 days (CI 37-57d), and median OS 97 days (CI 79-127d). Grade 3-5 toxicities included: hematologic 13% (G3), fatigue 12%, bleeding 6% (G3), nausea 4% (G3), Thrombosis/embolism 2% (G3), TTP/renal failure 2%, GI perforation 2% (G5). CONCLUSIONS: Preliminary analysis of a large cooperative group phase II study of S in previously-treated PAC suggests modest single agent activity and no new safety signals in this patient population. Final results will be presented. [Table: see text].

Duke Scholars

Author Donna Niedzwiecki Biostatistics & Bioinformatics, Division of Biostatistics