Overview

This trial is active, not recruiting.

Condition colon cancer
Treatments vigil™ vaccine, placebo
Phase phase 2
Sponsor Gradalis, Inc.
Start date March 2012
End date December 2016
Trial size 60 participants
Trial identifier NCT01505166, CL-PTL 107

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking single blind (subject)
Primary purpose treatment
Arm
(Experimental)
Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.
vigil™ vaccine formerly known as FANG™
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).
(Placebo Comparator)
Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.
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).
(Experimental)
Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).
vigil™ vaccine formerly known as FANG™
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).

Primary Outcomes

Measure
Overall Survival Rate
time frame: 24 Months

Secondary Outcomes

Measure
Immune Response
time frame: baseline, Month 2, 3, and 4

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histologically confirmed colorectal carcinoma with synchronous or metachronous liver metastases +/- pulmonary metastases. 2. Part 1 patients: May have multiple number of metastatic lesions as long as they can be rendered no evidence of disease (NED). 3. Part 2 patients: Maximum total number of metastatic lesions 4 month survival probability. 12. Normal organ and marrow function as defined below: Absolute granulocyte count ≥1,500/mm3 Absolute lymphocyte count ≥ 500/mm3 Platelets ≥100,000/mm3 Total bilirubin

Additional Information

Official title Randomized Phase II Trial of Post-operative Adjuvant Chemotherapy ± FANG™ Autologous Tumor Cell Vaccine in Colorectal Carcinoma With Liver Metastases
Principal investigator Minal Barve, MD
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Gradalis, Inc..