Randomized Phase II Adjuvant Chemotherapy ± FANG™ in Colorectal Carcinoma With Liver Metastases

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.

Conditions

• Colon Cancer

Interventions

BIOLOGICAL

Vigil™ Vaccine

Patients will receive 1 x 10\^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

DRUG

Placebo

Patients will receive 1 x 10\^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Sponsors & Collaborators

• Gradalis, Inc.

  lead INDUSTRY

Principal Investigators

• Minal Barve, MD · Mary Crowley Cancer Research Centers

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-03-31

Primary Completion

2016-08-31

Completion

2016-08-31

Countries

• United States

Study Locations