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Randomized Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) for High Risk Stage III/IV Ovarian Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Ovarian Cancer

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Trial Information

Randomized Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) for High Risk Stage III/IV Ovarian Cancer


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine and compare time to recurrence (TTR)

Outcome Description:

To determine and compare time to recurrence (TTR) following the administration of bi-shRNAfurin and GMCSF autologous tumor cell (FANGTM) 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).

Outcome Time Frame:

Participants will be followed for life.

Safety Issue:

No

Principal Investigator

Minal Barve, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mary Crowley Cancer Research Center

Authority:

United States: Food and Drug Administration

Study ID:

CL-PTL 105

NCT ID:

NCT01309230

Start Date:

February 2011

Completion Date:

January 2016

Related Keywords:

  • Ovarian Cancer
  • stage III/IV
  • epithelial ovarian cancer
  • ovarian cancer
  • Adjuvant
  • Ovarian Neoplasms

Name

Location

Palm Beach Cancer InstituteWest Palm Beach, Florida  33401
Mary Crowley Cancer Research CentersDallas, Texas  75201