Trial of Adjuvant FANG™ Vaccine for High Risk Stage III/IV Ovarian Cancer (FANG Ovarian)

This is a Phase II 2:1 randomized study of adjuvant intradermal autologous FANG™ cancer vaccine which is being expanded to women with Stage III/IV epithelial ovarian cancer who attain a clinical complete response (including a post-treatment, prevaccination baseline serum CA-125 level of ≤ 20 units/ml) after surgical cytoreduction and a total of six courses of front-line (pre- and post or post-surgical) chemotherapy. The treatment arm will receive FANG™ vaccine (Group A) at a dose of 1.0 x 10f^7 cells/injection for minimum of 4 to a maximum of 12 vaccinations (based on number of vaccine doses manufactured and patient eligibility. The comparison arm (Group B) will be standard of care observational follow-up. At recurrence, patients in Group B will be stratified into cisplatin sensitive and -resistant groups and treated with second-line chemotherapy. The response rate and duration of response to second-line therapy in patients with or without prior FANG™ will be compared. Trial endpoints include time to recurrence (TTR), documentation of immune responses, and correlation of immune response and clinical effect.

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, the investigators designed a novel autologous whole cell vaccine, FANG™, 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 (i.e. antigen immunogen), 3) enhance effector potency, and 4) subvert endogenous cancer-induced immune resistance. The investigators have also completed the Phase I assessment of FANG™ vaccine in 21 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 74 vaccinations among all patients. Plasmid functionality, immune biomarker response, and preliminary evidence of anticancer activity have been observed. This is a Phase II 2:1 randomized study of adjuvant intradermal autologous FANG™ cancer vaccine (1.0 x 10^7 cells/injection; maximum of 12 vaccinations) in women with stage IIIC epithelial ovarian cancer who attain a clinical or pathologic complete response (including a post-treatment, prevaccination baseline serum CA-125 level of ≤ 20 units/ml) after primary surgical cytoreduction and a total of six courses of front-line (pre- and post- or post-surgical) chemotherapy. The comparison arm will be standard of care observational follow-up. At recurrence, patients will be stratified into cisplatin-sensitive and -resistant groups and treated with second-line chemotherapy. The response rate and duration of response to second-line therapy in patients with or without prior FANG™ will be compared. Trial endpoints include time to recurrence (TTR), documentation of immune responses, and correlation of immune response and clinical effect.

• Biological: FANG
  intradermal autologous FANG™ cancer vaccine (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)
• Drug: standard of care observational follow-up
  standard of care observational follow-up

• Experimental: Group A
  adjuvant intradermal autologous FANG™ cancer vaccine (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)
  Intervention: Biological: FANG
• Active Comparator: Group B
  standard of care observational follow-up
  Intervention: Drug: standard of care observational follow-up

Inclusion Criteria:

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

• Treatment naïve, high risk ovarian cancer stratified as follows:

  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 to 20 U/ml.
• Clinically defined CR (no cancer related symptoms, normal physical examination and CT scan abdomen/pelvis and chest x-ray, and CA-125 ≤ 20 U/mL) following completion of surgical debulking and 6 cycles platinum/taxane adjuvant or sandwiched chemotherapy. (Patients who complete surgery/chemotherapy with a CA-125 >20 U/mL pre-randomization have the option of being followed up to 2 months if serial CA-125 values continue to decrease.
• Availability of "golf-ball" size ~ 30 grams tissue at time of primary surgical debulking.
• Successful manufacturing of 4 vials of FANG™ vaccine.
• Recovered from all clinically relevant toxicities related to prior protocol specific therapy (including neuropathy ≤Grade 2).
• ECOG performance status (PS) 0-2 prior to tumor debulking laparotomy.
• ECOG performance status (PS) 0-1 prior to FANG™ vaccine administration.

• 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
• Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.
• Ability to understand and the willingness to sign a written informed consent document for tissue harvesting.
• Ability to understand and the willingness to sign a written informed protocol specific consent document.

Exclusion Criteria:

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

• Treatment naïve, high risk ovarian cancer stratified as follows:

  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 to 20 U/ml.
• Clinically defined CR (no cancer related symptoms, normal physical examination and CT scan abdomen/pelvis and chest x-ray, and CA-125 ≤ 20 U/mL) following completion of surgical debulking and 6 cycles platinum/taxane adjuvant or sandwiched chemotherapy. (Patients who complete surgery/chemotherapy with a CA-125 >20 U/mL pre-randomization have the option of being followed up to 2 months if serial CA-125 values continue to decrease.
• Availability of "golf-ball" size ~ 30 grams tissue at time of primary surgical debulking.
• Successful manufacturing of 4 vials of FANG™ vaccine.
• Recovered from all clinically relevant toxicities related to prior protocol specific therapy (including neuropathy ≤Grade 2).
• ECOG performance status (PS) 0-2 prior to tumor debulking laparotomy.
• ECOG performance status (PS) 0-1 prior to FANG™ vaccine administration.

• 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
• Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.
• Ability to understand and the willingness to sign a written informed consent document for tissue harvesting.
• Ability to understand and the willingness to sign a written informed protocol specific consent document.