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

This study is currently recruiting participants.
Verified March 2014 by Gradalis, Inc.
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.
ClinicalTrials.gov Identifier:
NCT01309230
First received: February 25, 2011
Last updated: March 11, 2014
Last verified: March 2014

February 25, 2011
March 11, 2014
February 2011
July 2014   (final data collection date for primary outcome measure)
To determine and compare time to recurrence (TTR) [ Time Frame: Participants will be followed for life. ] [ Designated as safety issue: No ]
  • To determine and compare time to recurrence (TTR) following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (FANG™) vaccine in high risk patients with Stage III/IV ovarian cancer NED following tumor debulking surgery and chemotherapy to standard of care post treatment observation.
  • To assess time to recurrence (TTR) in following the administration of bishRNAfurin and GMCSF autologous tumor cell (FANG™) vaccine in Group A and those being followed as per standard of care in Group B in the patient subset of Stage IIIc ovarian cancer NED following tumor debulking surgery and chemotherapy (descriptive statistics only).
To determine and compare time to recurrence (TTR) [ Time Frame: Participants will be followed for life. ] [ Designated as safety issue: No ]
• To determine and compare time to recurrence (TTR) following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (FANG™) vaccine in high risk patients with stage IIIc ovarian cancer NED following tumor debulking surgery and chemotherapy to standard of care post treatment observation.
Complete list of historical versions of study NCT01309230 on ClinicalTrials.gov Archive Site
Immune Function [ Time Frame: Blood will be collected at baseline, Months 2, 3, 4, and EOT ] [ Designated as safety issue: Yes ]
  • To identify and determine the effect of FANG™ autologous tumor cell vaccine on immune surrogate markers.
  • To assess the predictive potential of initial tumor infiltrating lymphocyte (TIL) and tumor associated macrophage (TAM) phenotypes.
  • To enlarge the safety database of FANG™ autologous tumor cell vaccine in patients with minimal disease.
Immune Function [ Time Frame: Blood will be collected at baseline, Months 2, 4, 6, 9, 12, 18 and EOT ] [ Designated as safety issue: Yes ]
  • To identify and determine the effect of FANG™ autologous tumor cell vaccine on immune surrogate markers in this group of patients.
  • To enlarge the safety database of FANG™ autologous tumor cell vaccine in patients with minimal disease.
Not Provided
Not Provided
 
Trial of Adjuvant FANG™ Vaccine for High Risk Stage III/IV Ovarian Cancer
Randomized Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) for High Risk Stage III/IV Ovarian Cancer

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 10^7 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Ovarian Cancer
  • 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
    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
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
January 2016
July 2014   (final data collection date for primary outcome measure)

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 completion of at least 5 but no more than 6 cycles platinum/taxane adjuvant or sandwiched 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-randomization have the option of being followed up to 2 months if serial CA-125 values continue to decrease at a rate of ≥50% per month.
  • 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:

  • Surgery involving general anesthesia, radiotherapy, or immunotherapy within 4 weeks prior to vaccination. Steroid therapy within 1 week prior to vaccination.
  • Patient must not have received any other investigational agents within 4 weeks vaccine administration.
  • Patients with history of brain metastases.
  • 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.
  • Prior splenectomy.
  • Prior malignancy (excluding nonmelanoma carcinomas of the skin and carcinoma in-situ cervix) 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 with known HIV.
  • Patients with chronic Hepatitis B and C infection.
  • Patients with uncontrolled autoimmune diseases.
  • Psychiatric, addictive, or any disorder which compromises ability to give truly informed consent for participation in this study or adequate compliance.
Female
18 Years and older
No
Not Provided
United States
 
NCT01309230
CL-PTL 105
Yes
Gradalis, Inc.
Gradalis, Inc.
Not Provided
Not Provided
Gradalis, Inc.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP