Randomized Phase II Adjuvant Chemotherapy ± FANG™ in Colorectal Carcinoma With Liver Metastases
Status:
Terminated
Trial end date:
2016-08-01
Target enrollment:
Participant gender:
Summary
Preliminary studies with a variety of vaccines suggest target accessibility (potential
immunogenicity) in a variety of solid tumors to immune directed approaches. In an effort to
overcome limitations of immunostimulatory cancer vaccines, Gradalis has designed a novel
autologous vaccine to address inability to fully identify cancer associated antigens, antigen
recognition by the immune system (i.e. antigen-->immunogen), effector potency, and
cancer-induced resistance. In an effort to overcome limitations of immunostimulatory cancer
vaccines, we designed a novel dual-modulatory autologous whole cell vaccine, Vigil™,
incorporating the rhGMCSF transgene and the bifunctional shRNAfurin (to block proprotein
conversion to active TGFb1 and b2) to 1) address the inability to fully identify cancer
associated antigens, 2) effect antigen recognition by the immune system, 3) enhance effector
potency, and 4) subvert endogenous cancer-induced immune resistance. We have also completed
the Phase I assessment of Vigil™ vaccine in 30 advanced solid tumor patients (1.0 x 10^7
cells/injection/month for a maximum of 12 vaccinations) who have not experienced any
significant adverse effects following 144 vaccinations, including 6 patients with colorectal
carcinoma. Plasmid functionality, immune biomarker response, and preliminary evidence of
anticancer activity have been observed. This is a two-part Phase II study of the Vigil™
autologous vaccine. Six patients will be enrolled into the Part 1 of the study to receive
intradermal autologous Vigil™ cancer vaccine (1.0 x 10^7 cells/injection; maximum of 12
vaccinations). Part 2 of the study will be a randomized Phase II study of sandwich or
adjuvant chemotherapy and intradermal autologous Vigil™ cancer vaccine (1.0 x 10^7
cells/injection; maximum of 12 vaccinations) versus sandwich or adjuvant chemotherapy and
placebo in patients with colorectal carcinoma with either synchronous or metachronous liver
metastases (CLM +/= pulmonary metastases) following resection +/= ablation with curative
intent.Sandwich therapy indicates a combination of both pre-operative and postoperative
chemotherapy as opposed to neo-adjuvant (all chemotherapy prior to surgery) or adjuvant (all
chemotherapy following surgery) therapy. A minimum harvest aliquot to produce 4 monthly
injections will be required for entry into the study. Patients in whom insufficient tissue
(<4 doses) is collected or whose vaccine fails manufacturing release criteria will not
receive vaccine.