Salvage Ovarian FANG™ Vaccine + Bevacizumab

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

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.

Study Overview

• Status: Completed
• Conditions: Stage IV Ovarian Cancer; Stage III Ovarian Cancer
• Intervention / Treatment: Biological: Vigil™ Vaccine; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vigil™ Vaccine; Patients will receive 1.0 x 10e7 cells via intradermal injection one day each cycle for a maximum of 12 doses as long as sufficient material is available and subject is clinically stable. Additionally, patients will receive bevacizumab 10 mg/kg intravenously (prior to Vigil™ administration) every 2 weeks (4 weeks=1 cycle).

Biological: Vigil™ Vaccine; Patients meeting eligibility criteria will receive Autologous Vigil™ vaccine will be supplied by Gradalis,Inc. Patients will receive 1.0 x 10e7 cells via intradermal injection one day each cycle for a maximum of 12 doses as long as sufficient material is available and subject is clinically stable. Additionally, patients will receive bevacizumab 10 mg/kg intravenously (prior to Vigil™ administration) every 2 weeks (4 weeks=1 cycle).; Other Names: formerly known as FANG™; bi-shRNA furin and GMCSF Augmented Autologous Tumor Cell Vaccine; Drug: Bevacizumab; Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.; Other Names: VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline.	Up to 12 months
Time to Progression	Time to progression (TTP) following bevacizumab integrated with Vigil vaccine in patients failing standard of care in study CL-PTL 105 or in those not otherwise qualifying after vaccine production. This will be measured from the treatment start date (date of first dose) to either the date the patient is first recorded as having disease recurrence (even if the patient went off treatment because of toxicity), or the date of death if the patient dies due to any causes before progression.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Alive Subjects	Survival status of patients after treatment was determined by following these patients up to 24 months.	24 months
Enzyme-Linked ImmunoSorbent Spot (ELISPOT)	To determine if subjects will have a positive (defined as >10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until 30 days after last dose.	Baseline, End of Treatment (30 days after last dose) up to 12 months

Collaborators and Investigators

• Sponsor: Gradalis, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 1, 2012
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer; Papillary Serous Ovarian Cancer; Endometrioid Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Vaccines; Bevacizumab
• Other Study ID Numbers: CL-PTL 112