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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Gradalis, Inc.
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.
ClinicalTrials.gov Identifier:
NCT01309230
First received: February 25, 2011
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

This is a Phase II open-label trial of maintenance FANG™ 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, FANG™, 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 FANG™ injection Months 2, 4, 6 and at EOT. The dates of the last dose of chemotherapy and the administration of FANG™ 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.


Condition Intervention Phase
Ovarian Cancer
Biological: FANG™
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gradalis, Inc.:

Primary Outcome Measures:
  • To determine and compare time to recurrence (TTR) [ Time Frame: Participants will be followed for life. ] [ Designated as safety issue: No ]

    Primary Objective(s):

    • To assess time to recurrence (TTR) following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (FANG™) vaccine.



Secondary Outcome Measures:
  • Immune Function [ Time Frame: Blood will be collected at baseline, Months 2, 4, 6, and EOT ] [ Designated as safety issue: Yes ]

    Secondary Objectives:

    • 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.


Estimated Enrollment: 50
Study Start Date: February 2011
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FANG™
intradermal autologous FANG™ (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)
Biological: FANG™
intradermal autologous FANG™ (1.0 x 10^7 cells/injection; maximum of 12 vaccinations)

Detailed 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, FANG™, 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 FANG™ 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 FANG™ 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  1. Histologically confirmed Stage III/IV papillary serous or endometroid 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 to 20 U/ml
    3. IP chemotherapy versus IV chemotherapy
  3. 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. 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-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.
  4. Availability of "golf-ball" size ~10-30 grams tissue at time of primary surgical debulking.
  5. Successful manufacturing of 4 vials of FANG™ vaccine.
  6. Recovered from all clinically relevant toxicities related to prior protocol specific therapy (including neuropathy ≤ Grade 2).
  7. ECOG performance status (PS) 0-2 prior to tumor debulking laparotomy.
  8. ECOG performance status (PS) 0-1 prior to FANG™ vaccine administration.
  9. Normal organ and marrow function as defined below:

    1. Absolute granulocyte count ≥ 1,500/mm^3
    2. Absolute lymphocyte count ≥ 200/mm^3
    3. Platelets ≥ 75,000/mm^3
    4. Total bilirubin ≤ 2 mg/dL
    5. AST(SGOT)/ALT(SGPT) ≤ 2x institutional upper limit of normal
    6. Creatinine <1.5 mg/dL
  10. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.
  11. Ability to understand and the willingness to sign a written informed consent document for tissue harvesting.
  12. Ability to understand and the willingness to sign a written informed protocol specific consent

EXCLUSION CRITERIA:

  1. Surgery involving general anesthesia, radiotherapy, or immunotherapy within 4 weeks prior to randomization. Chemotherapy within 3 weeks prior to FANG™ 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309230

Locations
United States, Florida
Florida Cancer Specialists Recruiting
West Palm Beach, Florida, United States, 33401
Contact: Jenifer Bar-Nur, RN, BSN    561-472-1278    jbar-nur@flcancer.com   
Principal Investigator: Daniel L Spitz, MD, FACP         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Kathy Phipps, CCRP    603-653-3537    kathy.j.phipps@hitchcock.org   
Principal Investigator: Leslie R. DeMars, MD         
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75230
Contact: Referral Office    972-566-3000    referral@marycrowley.org   
Principal Investigator: Minal Barve, MD         
Texas Oncology - Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Marnie Fisher, RN    214-370-1038    marnie.fisher@usoncology.com   
Principal Investigator: Erik Koon, MD         
Texas Oncology - Fort Worth Recruiting
Fort Worth, Texas, United States, 76104
Contact: Nori Sullivan, BSN, RN, CCRC    817-850-2010    nori.sullivan@usoncology.com   
Principal Investigator: Kenneth Hancock, MD         
United States, Washington
Cancer Care Northwest Recruiting
Spokane, Washington, United States, 99202
Contact: Rose Miller, RN, OCN    509-228-1687    Rose.Miller@ccnw.net   
Principal Investigator: Elizabeth Grosen, MD         
Sponsors and Collaborators
Gradalis, Inc.
  More Information

Publications:
Responsible Party: Gradalis, Inc.
ClinicalTrials.gov Identifier: NCT01309230     History of Changes
Other Study ID Numbers: CL-PTL 105
Study First Received: February 25, 2011
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gradalis, Inc.:
Stage III
Stage IV
epithelial ovarian cancer
ovarian cancer
Adjuvant
immunotherapy

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on September 16, 2014