Abstract CT216: Phase I/IIa non-randomized open-label trials with mouse renal adenocarcinoma (RENCA) cell containing agarose-agarose macrobeads in patients with treatment-resistant metastatic colorectal carcinoma
Authors: Ocean Allyson J. , Berman Nathaniel , Parikh Tapan , Andrada Zoe P. , Nazarian Angelica , Thomas Joanne , Akahoho Eugene , Stoms George , Yaroshinsky Alex , Fahey Thomas J. , Wolf David J. , Gazda Lawrence S. , Smith Barry H. 
Published: August 2015

Abstract
Background: The purpose of phase I/IIa trials of RENCA tumor cells encapsulated in two concentric agarose layers is to evaluate safety and efficacy of agarose-agarose MB in various cancers, particularly advanced colorectal cancer (CRC) as reported in this abstract. MB release signals that inhibit tumor growth at primary or metastatic tumor locations. This novel approach has been substantiated in in vitro and in vivo models as reported in Cancer Research 71(3), 716-735, 2011. We report results of phase I/IIa studies in advanced metastatic CRC patients.
Methods: CRC patients who have progressive disease after all available treatment modalities with ECOG PS of 0-2 were enrolled to the trial after informed consents were obtained. Patients underwent laparoscopic intraperitoneal implantations up to 4 times with 8 (43/46 patients- established dose) or 16 (3/46 patients) RENCA MB/kg. Serial clinical examinations, blood tests, and imaging were obtained before and 3 months (mo.) after implantations to assess safety and efficacy. Endpoints of safety as measured by description of adverse events, and efficacy as measured by tumor marker response, were noted.
Results: 46 pts were implanted with RENCA MB (12 pts phase I; 34 pts phase II); of which 18 were males and 28 were females. Mean age was 58.2 years. 29/46 pts had a total of 1 implant (14 had a total of 2 implants; 1 had a total of 3 implants; 2 had a total of 4 implants). Response to MB is marked by a prominent initial rise in CRP, ESR, and IL-6, indicating a systemic inflammatory response (SIR) (100% of pts) and a parallel decrease in CEA and/or CA 19-9 in approximately 72%. SIR including its accompanying fatigue and anorexia lasts days to 3 wks. Overall, there was a significant difference in OS between the 72% of pts showing a decrease in tumor markers by at least 20% during the first 30 days post-implant (mean OS; 10.76 mo.) and those who did not (mean OS; 4.9 mo.). On PET-CT imaging, an important feature of response, most often seen in patients with the longest survival, was tumor necrosis. MB were well-tolerated. No Grade ≥3 adverse events were determined to be treatment-related.
Conclusions: In reported phase I/IIa trials in advanced, metastatic, treatment-resistant CRC patients, response to RENCA MB after implantation was characterized by decrease in tumor markers in association with SIR. This response was correlated with a significant increase in OS. RENCA MB represent a possible new therapeutic option for advanced, metastatic CRC.
Citation Format: Allyson J. Ocean, Nathaniel Berman, Tapan Parikh, Zoe P. Andrada, Angelica Nazarian, Joanne Thomas, Eugene Akahoho, George Stoms, Alex Yaroshinsky, Thomas J. Fahey, David J. Wolf, Lawrence S. Gazda, Barry H. Smith. Phase I/IIa non-randomized open-label trials with mouse renal adenocarcinoma (RENCA) cell containing agarose-agarose macrobeads in patients with treatment-resistant metastatic colorectal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT216. doi:10.1158/1538-7445.AM2015-CT216