A Trial of FANG™ Vaccine for Participants With Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Vigil™
Intervention description: 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 MeSH terms: Immunomodulating Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants were randomized 2 (Group A (Vigil)):1 (Group B (Standard of Care)). Randomization was only applicable to participants enrolled prior to approval of Protocol Amendment 8, dated June 19, 2014. All participants enrolled after approval of Protocol Amendment 8 were assigned to Group A (Vigil).
Masking: None (Open Label)
Enrollment: 145.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage III; Stage IV; epithelial ovarian cancer; ovarian cancer; Adjuvant bi-shRNAfurin and GMCSF; immunotherapy; Vigil; FANG; Autologous Tumor Cell Vaccine

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.
    

Eligibility criteria:

        Tissue 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.

        Tissue 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.

        Study Enrollment Inclusion Criteria

        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.

        Study Enrollment Exclusion Criteria

        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.