A phase II, multi-center study of a new non-cytotoxic A3 adenosine receptor agonist CF101, dose-finding (randomized blinded) in patients (pts) with refractory metastatic colorectal cancer

13082 Background: The A3 adenosine Gi protein-coupled receptor is highly expressed in malignant compared to normal cells. Activating the A3 adenosine receptor (A3AR) with the highly selective non-cytotoxic agonist, CF101 (IB-MECA), inhibit of colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models, via down-regulation of the Wnt and NF-κB signal transduction pathways. Oral CF101 has been shown to inhibit colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models. Methods: A phase II dose-finding, randomized, blinded study of oral CF101 (0.1, 1& 4 mg PO BID), was conducted to define activity and safety in heavily pre-treated metastatic colorectal cancer pts. From 6/1/2003–7/4/2004, 70 pts, median age 62 with measurable colorectal cancer, PS ≤2 were enrolled, 21 pts progressed after irinotecan and 49 pts after both irinotecan and oxaliplatin-based regimens. Results: The median time on treatment was 10.3 weeks. No objective response was observed; however, SD for 8 wks duration was achieved in 24 pts (34%), for 16 weeks in 8 pts (11%) and 2 pts were treated for more than 24 weeks. The median time to treatment progression was 72 days and for overall survival was 254 days without any significant difference among the 3 trial doses [8 survivors till today]. There were no obvious treatment related serious adverse events. Conclusions: The final results of the study show that CF101 is well tolerated and may stabilize disease for at least 2 months in 35% of the pts. The median survival time (8 months) compared with other targeted therapy investigated lately is encouraging. Combining CF101 with chemotherapy may be beneficial in the treatment of metastatic colorectal cancer. No significant financial relationships to disclose.