This trial is active, not recruiting.

Condition ovarian cancer
Treatment vigil™
Phase phase 2
Sponsor Gradalis, Inc.
Start date February 2011
End date January 2017
Trial size 44 participants
Trial identifier NCT01309230, CL-PTL 105


This is a Phase II open-label trial of maintenance Vigil™ autologous tumor cell vaccine. Tumor will be harvested at the time of surgical debulking (standard of medical care). Subsequently, patients achieving clinical CR following primary surgical debulking and doublet chemotherapy will be stratified for i) surgical stage (Stage IV or suboptimal debulking (>1 cm residual) Stage III disease versus Stage III patients with optimal debulking (<1 cm residual)) and ii) post-op chemotherapy, pre-vaccine CA-125 >10 ≤ 20 U/mL versus 0≤10 U/ml. (Note: patients with Stage IIIc ovarian cancer will be additionally evaluated as a subset using descriptive statistics only). Patients will receive 1.0 x 10^7 cells / intradermal injection of gene transfected autologous tumor cells, Vigil™ once a month for up to 12 doses as long as sufficient material is available. Enough harvested tissue to provide a minimum of 4 monthly injections will be required for entry into the study. Hematologic function, liver enzymes, renal function and electrolytes will be monitored monthly. Immune function analysis including ELISPOT analysis of cytotoxic T cell function to autologous tumor antigens will be monitored at (≤24 hours before) tissue harvest, ≤24 hours before the first cycle of chemotherapy (post debulking), ≤24 hours before the third cycle of chemotherapy (post debulking), baseline (screening), prior to Vigil™ injection Months 2, 4, 6 and at EOT. The dates of the last dose of chemotherapy and the administration of Vigil™ vaccine #1 will be recorded. Treatment will be continued 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) develops related to study treatment the vaccine dose will be reduced by 50% and continued on a monthly basis. If a single patient develops ≥ Grade 3 toxicity (other than injection site reaction) related to study treatment the trial will be placed on hold for reevaluation of design in discussion with FDA. During this hold, no new subjects will initiate dosing, but subjects already being dosed may continue dosing as scheduled if deemed clinically appropriate by the PI.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
intradermal autologous Vigil™ (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)
vigil™ formerly known as FANG™
intradermal autologous Vigil™ (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)

Primary Outcomes

To determine and compare time to recurrence (TTR)
time frame: Participants will be followed for life.

Secondary Outcomes

Immune Function
time frame: Blood will be collected at baseline, Months 2, 4, 6, and EOT

Eligibility Criteria

Female participants at least 18 years old.

Tissue Procurement Inclusion Criteria: 1. Presumptive Stage III/IV papillary serous or endometrioid ovarian cancer. 2. Per Amendment #8, treatment naïve, high risk ovarian cancer will no longer be stratified, but the following information will be 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. INCLUSION 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 complete at least 5 but no more than 6 cycles platinum/taxane adjuvant or interval debulking + chemotherapy (or chemotherapy as per recommendations of NCCN guidelines, category 1 (IP chemotherapy included)). (Patients who complete surgery/chemotherapy with a CA-125 >20 U/mL pre-registration have the option of being followed up to 2 months if serial CA-125 values continue 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 be 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: 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. Patient must not have received any other investigational agents within 4 weeks 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) are permitted; other steroid regimens and/or immunosuppressives are 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 limit compliance with study requirements 10. Patients with known HIV. 11. Patients with chronic Hepatitis B and C infection. 12. Patients with uncontrolled autoimmune diseases.

Additional Information

Official title Open Label Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) for High Risk Stage III/IV Ovarian Cancer
Principal investigator Minal Barve, MD
Description Despite a gradual improvement in their overall survival over the past decade, approximately 75% of women with Stage IIIC ovarian cancer who achieve a complete clinical response will relapse as will 50% of those achieving pathologic complete response at a median time of 18-24 months. Phase III studies of both maintenance and consolidation therapeutic interventions have not translated into an overall survival advantage. Preliminary studies of immunotherapy in patients with ovarian cancer suggest target accessibility (potential immunogenicity) to immune mediated approaches. In an effort to overcome limitations of immunostimulatory cancer vaccines, we designed a novel autologous whole cell vaccine, Vigil™, incorporating the rhGMCSF transgene and the bifunctional shRNA^furin (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 (i.e. antigen→immunogen), 3) enhance effector potency, and 4) subvert endogenous cancer-induced immune resistance. A Phase I assessment of Vigil™ vaccine in 33 advanced solid tumor patients (1 of them being a pediatric patient 15 years of age) receiving ≥1 vaccination (at a dose of 1.0 x 10^7 or 2.5 x 10^7 cells/injection/month for a maximum of 12 vaccinations) demonstrated safety of the Vigil™ vaccine. Furthermore, proof of principle was established in the manufactured vaccines with increased mean GMCSF expression post-transfection to 1135 pg/10^6 cells/ml and knockdown of furin, TGFb1 and TGFb2 at 78%, 93%, and 95%, respectively). In addition, although a Phase I study, the data suggested an overall survival benefit.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Gradalis, Inc..