Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer

NCT01061840 | Completed Phase 1 DMC

• 1 other identifier: CL-PTL-101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

Autologous Vigil™ vaccine expresses rhGMCSF and bi-shRNAfurin from the Vigil™ plasmid. The GMCSF protein is a potent stimulator of the immune system, recruiting immune effectors to the site of intradermal injection and promoting antigen presentation. The furin bifunctional shRNA blocks furin protein production at the post transcriptional and translational levels. This decrease in furin in turn decreases the conversion of the proforms TGFβ1 and TGFβ2 proteins. Also, reduced furin protein levels have a negative feedback inhibition on TGFβ1 and TGFβ2 gene expression, decreasing the levels of their mRNAs. The resulting decrease in TGFβ1 and TGFβ2 proteins reduces the local immunosuppression they cause and promotes tumor surface antigen and MHC protein display.

Conditions

Ewings Sarcoma; Non Small Cell Lung Cancer; Liver Cancer

Keywords

Ewings Sarcoma; Non Small Cell Lung Cancer; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• To determine safety following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (Vigil™) vaccine in advanced solid tumor patients who have no acceptable form of standard therapy with curative intent.

  Participants will be followed for life

Secondary Outcomes (1)

• To determine time to progression. To evaluate the effect of Vigil™ vaccine on immune stimulation. To evaluate whether lower cell doses would activate ELISPOT responses and to compare durability of dose elicited responses.

  Participants will be followed for life.

Study Arms (3)

1 x 10 ^7 cells/injection

EXPERIMENTAL

Vigil™

Biological: Vigil™

2.5 x 10 ^7 cells/injection

EXPERIMENTAL

Vigil™

Biological: Vigil™

1 x 10^6 or 4 x 10^6 cells/injection

EXPERIMENTAL

Vigil™

Biological: Vigil™

Interventions

Vigil™ BIOLOGICAL

Patients will be treated once a month as long as sufficient material is available for up to 12 doses

Also known as: bi-shRNAfurin and GMCSF Augmented Autologous Tumor, Cell Vaccine, formerly known as FANG™ Vaccine

1 x 10 ^7 cells/injection

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Presumptive or histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion, and may not be a candidate for curative surgery or radiation therapy).
• For the purpose of the Pediatric study patients with histologic diagnosis of ESFT including: Ewing's sarcoma or primitive neuroectodermal tumor (malignant neuroepithelioma) of the bone or soft tissues, Askin's tumor of the chest and with central nervous system tumors are eligible.
• Patients with recurrent or refractory ESFT. Patients with de novo poor prognosis/high risk ESFT: (Eligible for vaccine manufacturing at diagnosis but ONLY ELIGIBLE FOR IMMUNOTHERAPY IF DEMONSTRATES PERSISTENT/RECURRENT/ REFRACTORY DISEASE)
• Large tumors \> 8 cm
• Pelvic osseous tumors ANY SIZE
• Bilateral pulmonary metastasis
• \>2 unilateral pulmonary metastasis
• Clinically (medically) indicated procedure (i.e. biopsy of lesions of recurrent disease, palliative management via resection, thoracentesis, etc.) to collect tumor in sufficient quantity ("golf ball size" estimated weight 10-30 grams, pleural, and/or ascites fluid estimated volume ≥ 500 mL) for vaccine processing.
• For ESFT patients age ≥12 years.
• Age ≥18 years (non-ESFT candidates) ECOG performance status (PS) 0-1. Pediatric patients with Lansky or Karnofsky Performance Status Scale ≥ of 50%.
• Estimated \>4 months survival probability.
• Ability to understand and the willingness to sign a written informed consent document. Pediatric patients must sign an assent with a parent or legal guardian sign a written informed consent.
• Histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion may not be a candidate for curative surgery or radiation therapy). Successful vaccine manufacture has resulted from tissue/fluid obtained from the following major organ systems: digestive, endocrine, reproductive, respiratory, and urinary.Individuals manufactured under CL-PTL 105 (Phase II Ovarian) may be eligible for enrollment without advanced or metastatic disease.
• Patients with well differentiated thyroid cancer are eligible for protocol as follows:
• Surgically unresectable locally recurrent disease and/or metastatic disease following RAI ablation (if locally recurrent and ultrasound (US) positive, baseline FDG-PET or MRI will be obtained).

You may not qualify if:

• Surgery involving general anesthesia, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to vaccination. Chemotherapy within 3 weeks prior to entering the study. Palliative radiotherapy is allowable. Collection of lumenal tissue for vaccine manufacture must be avoided.
• Patients must not have received any other investigational agents within 30 days prior to vaccination.
• Patients with known active or symptomatic brain metastases prior to vaccination.
• Patients with compromised pulmonary disease.
• Short term (\<30 days) concurrent systemic steroids ≤0.25 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded while receiving vaccine. Patients requiring steroids following previous CNS radiation for metastatic disease are excluded.
• Prior splenectomy unless Howell-Jolly bodies are absent.
• Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for 2 years.
• Kaposi's Sarcoma.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are pregnant or nursing.
• Patients with known HIV.
• Patients with uncontrolled autoimmune diseases.

Sponsors & Collaborators

• Gradalis, Inc.: lead

Study Sites (4)

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

Cancer Care Northwest

Spokane, Washington, 99202, United States

Location

Related Publications (6)

• Nemunaitis J, Barve M, Orr D, Kuhn J, Magee M, Lamont J, Bedell C, Wallraven G, Pappen BO, Roth A, Horvath S, Nemunaitis D, Kumar P, Maples PB, Senzer N. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG) in advanced cancer of the liver. Oncology. 2014;87(1):21-9. doi: 10.1159/000360993. Epub 2014 Jun 25.

  PMID: 24968881 BACKGROUND

• Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther. 2012 Mar;20(3):679-86. doi: 10.1038/mt.2011.269. Epub 2011 Dec 20.

  PMID: 22186789 RESULT

• Ghisoli M, Barve M, Mennel R, Lenarsky C, Horvath S, Wallraven G, Pappen BO, Whiting S, Rao D, Senzer N, Nemunaitis J. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1478-83. doi: 10.1038/mt.2016.86. Epub 2016 Apr 25.

  PMID: 27109631 RESULT

• Ghisoli M, Barve M, Schneider R, Mennel R, Lenarsky C, Wallraven G, Pappen BO, LaNoue J, Kumar P, Nemunaitis D, Roth A, Nemunaitis J, Whiting S, Senzer N, Fletcher FA, Nemunaitis J. Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma. Mol Ther. 2015 Jun;23(6):1103-1109. doi: 10.1038/mt.2015.43. Epub 2015 Mar 19.

  PMID: 25917459 RESULT

• Oh J, Barve M, Senzer N, Aaron P, Manning L, Wallraven G, Bognar E, Stanbery L, Horvath S, Manley M, Nemunaitis J, Walter A, Rocconi RP. Long-term follow-up of Phase 2A trial results involving advanced ovarian cancer patients treated with Vigil(R) in frontline maintenance. Gynecol Oncol Rep. 2020 Sep 17;34:100648. doi: 10.1016/j.gore.2020.100648. eCollection 2020 Nov. No abstract available.

  PMID: 33364285 RESULT

• Rocconi RP, Stanbery L, Madeira da Silva L, Barrington RA, Aaron P, Manning L, Horvath S, Wallraven G, Bognar E, Walter A, Nemunaitis J. Long-Term Follow-Up of Gemogenovatucel-T (Vigil) Survival and Molecular Signals of Immune Response in Recurrent Ovarian Cancer. Vaccines (Basel). 2021 Aug 12;9(8):894. doi: 10.3390/vaccines9080894.

  PMID: 34452019 RESULT

MeSH Terms

Conditions

Sarcoma, Ewing; Carcinoma, Non-Small-Cell Lung; Liver Neoplasms

Interventions

FANG vaccine

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Minal Barve, MD

  Mary Crowley Cancer Research Centers

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2010
• First Posted: February 3, 2010
• Study Start: December 1, 2009
• Primary Completion: December 6, 2018
• Study Completion: January 1, 2019
• Last Updated: March 15, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)