Clinical trial NCT01551745: Salvage Ovarian FANG™ Vaccine + Bevacizumab
Official title: Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) Integrated With Bevacizumab for Patients With Recurrent/Refractory Ovarian Cancer Participating in Study CL-PTL 105
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Keywords: Papillary Serous Ovarian Cancer
Endometrioid Ovarian Cancer
Epithelial Ovarian Cancer
Lead sponsor: Gradalis, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-13
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase II study of Vigil™ autologous tumor cell vaccine integrated with bevacizumab. All patients will have had Vigil™ prepared and stored from initial primary surgical debulking. Patients meeting eligibility criteria will receive Vigil™ 1.0 x 10e7 cells/intradermal injection once every 4 weeks and bevacizumab 10 mg/kg intravenously every 2 weeks.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed papillary serous or endometrioid ovarian cancer.
2. Previous randomization to Gradalis, Inc. protocol CL-PTL 105; observation arm (Group B) or patients with vaccine prepared for CLPTL 105 but not otherwise qualifying.
3. Recurrent cisplatinum resistant/refractory disease (defined as the appearance of any measurable or evaluable lesion or as asymptomatic CA-125 levels greater than 100 u/mL at two consecutive measurements with no intervening therapy.
4. Successful manufacturing of 4 vials of Vigil™ vaccine.
5. Recovered from all clinically relevant toxicities related to prior therapies.
6. ECOG PS 0-2 prior to Vigil™ vaccine administration.
7. Normal organ and marrow function as defined below:

   1. Absolute granulocyte count ≥1,500/mm3
   2. Absolute lymphocyte count ≥ 200/mm3
   3. Platelets ≥100,000/mm3
   4. Total bilirubin ≤1.5 x ULN
   5. AST(SGOT)/ALT(SGPT)/alkaline phosphatase ≤2.5 x ULN
   6. Creatinine \<1.5 mg/dL
   7. INR \< 1.5
8. Baseline blood pressure must be under 140/90
9. Urine protein-to-creatinine ratio \< 1.0 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 protocol specific consent.

Exclusion Criteria:

1. Surgery involving general anesthesia, chemotherapy, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to vaccination. Chemotherapy within 3 weeks prior to vaccination. Steroid therapy within 1 week prior to vaccination.
2. Major surgery within 6 weeks or minor surgery within 2 weeks of receiving bevacizumab.
3. Patient must not have received any other investigational agents within 4 weeks prior to study entry.
4. Patients who require parenteral hydration of nutrition and have evidence of partial bowel obstruction or perforation.
5. Patients with history of brain metastases.
6. Patients with compromised pulmonary disease.
7. 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.
8. Prior splenectomy.
9. Prior malignancy (excluding nonmelanoma carcinomas of the skin and carcinoma in situ cervix) unless in remission for ≥ 2 years.
10. Kaposi's Sarcoma.
11. Patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major blood vessels.
12. History of Stroke/Transient Ischemic Attack
13. Use of bleeding diathesis
14. Use of anti-coagulants
15. Patients with clinically significant cardiovascular disease including any of the following:

    1. Significant cardiac conduction abnormalities (e.g., PR interval \> 0.24 sec or second or third degree AV block.
    2. Uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg.
    3. Myocardial infarction, cardiac arrhythmia, or unstable angina within the past 6 months.
    4. New York Heart Association grade II or greater congestive heart failure.
    5. Serious cardiac arrhythmia requiring medication.
    6. Grade II or greater peripheral vascular disease except episodes of ischemia \< 24 hours induration that are managed non-surgically and without permanent deficit
    7. History of cerebrovascular accident within the past 6 months.
    8. No significant traumatic injury within the past 28 days.
16. Uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
17. Patients with known HIV.
18. Patients with chronic Hepatitis B and C infection.
19. Patients with uncontrolled autoimmune diseases.

Primary outcomes:
measure: Time to Progression
timeFrame: 24 months
measure: Response Rate
timeFrame: Up to 12 months
Secondary outcomes:
measure: Number of Alive Subjects
timeFrame: 24 months
measure: Enzyme-Linked ImmunoSorbent Spot (ELISPOT)
timeFrame: Baseline, End of Treatment (30 days after last dose) up to 12 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers
state: Texas
Study officials:
affiliation: Mary Crowley Cancer Research Centers
name: Minal Barve, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.