Phase II study of CC-4047 in patients (pts) with metastatic hormone-refractory prostate cancer (HRPC)

Abstract

4629 Background: CC-4047 is a new analog of thalidomide with potent immunomodulatory and anti-angiogenesis properties. similar to thalidomide. This study investigates whether single agent CC-4047 can induce PSA responses and increase time to progression in HRPC. Eligibility included: histologically confirmed HRPC, 2 consecutive rises in prostate-specific antigen (PSA) with an absolute change of at least 1ng/ml separated by 28 days, with or without radiographic evidence of disease, castrate levels of serum testosterone (≤50 ng/dL), failure to androgen withdrawal, ≤1 prior chemotherapy regimen, ECOG performance status of ≤1, life expectancy ≥3 months, and normal organ/marrow function. Methods: CC-4047 was administered orally in doses of 1 or 2mg/day without interruption. Pts. are followed every 4 weeks with re-evaluation at week 12. Forty-four pts have been enrolled. Pt characteristics: 1mg dose level: 22 pts enrolled, median age 69 years (range 58–82). Fourteen pts with bone involvement only. Four pts with bone and nodal involvement. Four pts with nodal or visceral tumor involvement only. Median PSA 157 (0.8–313). 2mg dose level: 22 pts enrolled, median age 68 years (range 44–84). Seven pts with bone involvement only. Two pts with bone and nodal involvement. Five pts with bone and visceral involvement. Three pts with nodal or visceral tumor involvement. Four pts with prostate intact. Median PSA: 70 (0.6–139). Results: Of the 22 pts at 1mg, 20 pts have completed 12 weeks of therapy. One pt remains on study for 60+ weeks. PSA decreased in 6 pts, 3 pts with >50% decrease. Of the 22 pts at 2mg, 19 completed 12 weeks of therapy. Nine pts remain on study. PSA decreased in 9 pts, with 2 pts having a >50% reduction. Grade 1–2 toxicity included: constipation, nausea, vomiting, and fatigue. One Grade 3 toxicity consisting of nausea. One pt expired secondary to a CNS bleed while on therapeutic doses of coumadin. Of the 22 pts at 2mg, 16 completed 12 weeks of therapy. Nine pts remain on study. PSA decreased in 9 pts, with 2 pts having a >50% reduction. Conclusion: CC-4047 shows promising activity in pts with HRPCa, with an acceptable tolerability. Response, progression-free survival and toxicity data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene, Chiron Celgene, Chiron, Endocyte