A Trial of FANG™ Vaccine for Participants With Ovarian Cancer

NCT ID: NCT01309230

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-08
• Study Completion Date: 2022-02-02

Brief Summary

This was a clinical trial for women with ovarian cancer scheduled to have an operation to remove the cancerous tissue. The cancer cells removed during the planned surgery were used to attempt to make the investigational product, named Vigil. Vigil is considered an immunotherapy. In this study, participants who met the requirements to be in the study and if Vigil was successfully made from the participants cancer cells, participants underwent treatment with their standard chemotherapy regimen. At the end of the standard chemotherapy regimen and if there was no evidence of remaining cancer, participants were randomly assigned to receive the Vigil or would be assigned to the standard of care group, which in this study meant no further treatment was given to the participant.

The purpose of this study was to compare the difference between the participants who received Vigil versus the usual care after completion of standard chemotherapy and to determine if Vigil delayed or prevented ovarian cancer from coming back.

Detailed Description

This was a Phase II open-label study of Vigil™ autologous tumor cell vaccine trial administered to women with Stage III/IV epithelial ovarian cancer. Tumor was harvested at the time of surgical debulking (standard of medical care). Participants who achieved clinical complete response (CR) following primary surgical debulking and front-line doublet chemotherapy were randomized 2:1 to either treatment with Vigil (Group A) or standard of care without maintenance therapy (Group B). After randomization, participants were stratified into cohorts by baseline CA-125 (greater than 10 to less than 20 units/mL versus less than or equal to 10 units/mL). For data analysis, participants could further be stratified by surgical stage (Stage IV or suboptimal debulking (> 1cm residual), Stage III disease versus Stage III disease with optimal debulking (< 1cm residual). Participants enrolled in Group A (Vigil) received 1.0 x 10e7 cells / intradermal injection of gene transfected autologous tumor cells, Vigil™, once a month for up to 12 doses as long as sufficient material was available or until trial endpoints were met. Enough harvested tissue to provide a minimum of 4 monthly injections was required for entry into the study. Participants enrolled in Group B (Standard of Care, SOC) were observed and assessed until trial endpoints were met. Protocol Amendment 8, June 19, 2014 removed randomization such that all patients screening for enrollment into the main portion of the trial (including those who previously had tumor tissue harvested) would be assigned to Group A (Vigil).

Both groups of participants were seen once a month in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes were monitored monthly. Immune function analysis including ELISPOT analysis of cytotoxic T cell function to autologous tumor antigens were monitored at (≤ 24 hours before the third cycle chemotherapy (post debulking), baseline (screening); prior to Vigil injection at Months 2, 3, 6 and EOT. CA-125 was monitored at baseline, every month for the first year, every 3 months +/- 2 weeks for the second and third year.

Participants assigned to group A were allowed to continue treatment with Vigil until disease recurrence or exhaustion of the patient's vaccine supply. If ≥ Grade 2 toxicity by NCI Common Toxicity Criteria (excluding Grade 2 fever ≤ 24 hours and Grade 2 and 3 injection site reactions) developed related to study treatment, the vaccine dose was reduced by 50% and continued on a monthly basis.

Efficacy assessments included time to disease recurrence, immune surrogate markers, and quality of life questionnaire (FACT-O, Version 4). Safety assessments included physical examination, performance status, and vital signs. Adverse events were recorded using CTCAE version 3.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A (Vigil™)

Vigil immunotherapy was administered at a concentration of at 1 x 10e7 cells/injection via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting ≥3 weeks following completion of chemotherapy (no longer than 2.5 months post chemotherapy). Participants were treated monthly for up to 12 months as long as sufficient Vigil was available and the participant was clinically stable.

Group Type: EXPERIMENTAL

Vigil™

Intervention Type: BIOLOGICAL

Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.

Group B (Observational - Standard of Care)

Participants received standard of care without maintenance therapy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Vigil™

Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.

Intervention Type: BIOLOGICAL

Other Intervention Names

formerly known as FANG™ vaccine; Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy

Eligibility Criteria

Inclusion Criteria

Patients were eligible for tissue procurement for the Vigil™ vaccine manufacturing process if they met all of the following criteria:

1. Presumptive Stage III/IV papillary serous or endometrioid ovarian cancer.

2. Per Amendment #8, treatment naïve, high risk ovarian cancer was no longer be stratified, but the following information was collected:

1. Stage IV or suboptimal (>1 cm residual) Stage III disease versus Stage III patients with optimal (≤1 cm residual) disease,

2. CA-125 ≤10 U/ml versus CA-125 greater than 10 but less than or equal to 20 U/ml

3. IP chemotherapy versus IV chemotherapy

3. Availability of "golf-ball" size 10-30 grams tissue at time of primary surgical debulking.

4. ECOG performance status (PS) 0-2 prior to tumor debulking laparotomy

5. Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

Patients were registered for inclusion in this study if they met all of the following criteria:

1. Histologically confirmed Stage III/IV papillary serous or endometrioid ovarian cancer.

2. Clinically defined CR (no cancer related symptoms, normal physical examination and CT scan abdomen/pelvis and CXR, and CA-125 ≤20 U/ml) following completion of primary surgical debulking. Patients enrolled must have completed at least 5 but no more than 6 cycles platinum/taxane adjuvant or interval debulking and chemotherapy (or chemotherapy as per recommendations of NCCN guidelines, category 1 (IP chemotherapy included)). (Patients who completed surgery/chemotherapy with a CA-125 >20 U/mL pre-registration had the option of being followed up to 2 months if serial CA-125 values continued to decrease at a rate of CA-125 decrease of ≥ 50% per month.)

3. Successful manufacturing of 4 vials of Vigil™ vaccine

4. Recovered from all clinically relevant toxicities related to prior protocol specific therapies (including neuropathy to ≤Grade 2).

5. ECOG performance status (PS) 0-1.

6. Normal organ and marrow function as defined below:

Absolute granulocyte count ≥ 1,500/mm3 Absolute lymphocyte count ≥ 200/mm3 Platelets ≥ 75,000/mm3 Total bilirubin ≤ 2 mg/dL AST(SGOT)/ALT(SGPT) ≤ 2x institutional upper limit of normal Creatinine < 1.5 mg/dL

7. Patients must have been off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.

8. Ability to understand and the willingness to sign a written informed protocol specific consent document.

Exclusion Criteria

Patients who met any of the following criteria were not eligible for tissue procurement for the Vigil manufacturing:

1. Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for < 30 days duration.

2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers were allowed if definitively resected.

3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.

4. Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.

5. Known HIV or chronic Hepatitis B or C infection.

6. Known history of allergies or sensitivities to gentamicin.

7. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or was not in the best interest of the patient to participate, in the opinion of the treating Investigator.

Patients were excluded from this study if they met any of the following criteria:

1. Surgery involving general anesthesia, radiotherapy, or immunotherapy within 4 weeks prior to randomization. Chemotherapy within 3 weeks prior to Vigil™ vaccine administration. Steroid therapy within 1 week prior to vaccine administration

2. Patients must not have received any other investigational agents within 4 weeks prior to Vigil™ vaccine administration.

3. Patients with history of brain metastases.

4. Patients with compromised pulmonary disease.

5. Short term (<30 days) concurrent systemic steroids ≤ 0.25 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) were permitted; patients requiring other steroid regimens and/or immunosuppressives at randomization were excluded.

6. Prior splenectomy.

7. Prior malignancy (excluding nonmelanoma carcinomas of the skin and carcinoma in situ cervix) unless in remission for ≥ 2 years.

8. Kaposi's Sarcoma.

9. 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 have limited compliance with study requirements.

10. Patients with known HIV.

11. Patients with chronic Hepatitis B and C infection.

12. Patients with uncontrolled autoimmune diseases.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gradalis, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Nemunaitis, MD

Role: STUDY_DIRECTOR

Gradalis, Inc.

Locations

Florida Cancer Specialists

West Palm Beach, Florida, United States

Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Texas Oncology - Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology - Fort Worth

Fort Worth, Texas, United States

Cancer Care Northwest

Spokane, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22186789 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24968881 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27109631 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25917459 (View on PubMed)

Ghisoli M, Rutledge M, Stephens PJ, Mennel R, Barve M, Manley M, Oliai BR, Murphy KM, Manning L, Gutierrez B, Rangadass P, Walker A, Wang Z, Rao D, Adams N, Wallraven G, Senzer N, Nemunaitis J. Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy. J Pediatr Hematol Oncol. 2017 May;39(4):e183-e186. doi: 10.1097/MPH.0000000000000822.

Reference Type: BACKGROUND

PMID: 28338569 (View on PubMed)

Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN, Tang M, Aaron P, Stanbery L, Horvath S, Wallraven G, Bognar E, Manning L, Nemunaitis J, Shanahan D, Slomovitz BM, Herzog TJ, Monk BJ, Coleman RL. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Oncol. 2020 Dec;21(12):1661-1672. doi: 10.1016/S1470-2045(20)30533-7.

Reference Type: BACKGROUND

PMID: 33271095 (View on PubMed)

Oh J, Barve M, Matthews CM, Koon EC, Heffernan TP, Fine B, Grosen E, Bergman MK, Fleming EL, DeMars LR, West L, Spitz DL, Goodman H, Hancock KC, Wallraven G, Kumar P, Bognar E, Manning L, Pappen BO, Adams N, Senzer N, Nemunaitis J. Phase II study of Vigil(R) DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynecol Oncol. 2016 Dec;143(3):504-510. doi: 10.1016/j.ygyno.2016.09.018. Epub 2016 Sep 24.

Reference Type: RESULT

PMID: 27678295 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33364285 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34452019 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CL-PTL 105

Identifier Type: -

Identifier Source: org_study_id