Salvage Ovarian FANG™ Vaccine + Bevacizumab

• Sponsor: Gradalis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01551745
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 49
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stage III Ovarian Cancer; Stage IV Ovarian Cancer	Biological: Vigil™ Vaccine; Drug: Bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Mar 1, 2012
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

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: bi-shRNA furin and GMCSF Augmented Autologous Tumor Cell Vaccine formerly known as FANG™ ; Drug: Bevacizumab; Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.; Other Names: VEGF

Outcome Measures

Primary Outcome Measures

1. Time to Progression [24 months]

   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.

2. Response Rate [Up to 12 months]

   Response will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline.

Secondary Outcome Measures

1. Number of Alive Subjects [24 months]

   Survival status of patients after treatment was determined by following these patients up to 24 months.

2. Enzyme-Linked ImmunoSorbent Spot (ELISPOT) [Baseline, End of Treatment (30 days after last dose) up to 12 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically confirmed papillary serous or endometrioid ovarian cancer.

2. Previous randomization to Gradalis, Inc. protocol CL-PTL 105; observation arm (Group

1. or patients with vaccine prepared for CLPTL 105 but not otherwise qualifying.

1. 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.

2. Successful manufacturing of 4 vials of Vigil™ vaccine.

3. Recovered from all clinically relevant toxicities related to prior therapies.

4. ECOG PS 0-2 prior to Vigil™ vaccine administration.

5. Normal organ and marrow function as defined below:

6. Absolute granulocyte count ≥1,500/mm3

7. Absolute lymphocyte count ≥ 200/mm3

8. Platelets ≥100,000/mm3

9. Total bilirubin ≤1.5 x ULN

10. AST(SGOT)/ALT(SGPT)/alkaline phosphatase ≤2.5 x ULN

11. Creatinine <1.5 mg/dL

12. INR < 1.5

13. Baseline blood pressure must be under 140/90

14. Urine protein-to-creatinine ratio < 1.0 mg/dL.

15. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.

16. 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:

16. Significant cardiac conduction abnormalities (e.g., PR interval > 0.24 sec or second or third degree AV block.

17. Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg.

18. Myocardial infarction, cardiac arrhythmia, or unstable angina within the past 6 months.

19. New York Heart Association grade II or greater congestive heart failure.

20. Serious cardiac arrhythmia requiring medication.

21. Grade II or greater peripheral vascular disease except episodes of ischemia < 24 hours induration that are managed non-surgically and without permanent deficit

22. History of cerebrovascular accident within the past 6 months.

23. No significant traumatic injury within the past 28 days.

24. Uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

25. Patients with known HIV.

26. Patients with chronic Hepatitis B and C infection.

27. Patients with uncontrolled autoimmune diseases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mary Crowley Cancer Research Centers	Dallas	Texas	United States	75230

Sponsors and Collaborators

• Gradalis, Inc.

Investigators

• Principal Investigator: Minal Barve, MD, Mary Crowley Cancer Research Centers

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Gradalis, Inc.
• ClinicalTrials.gov Identifier: NCT01551745
• Other Study ID Numbers: CL-PTL 112
• First Posted: Mar 13, 2012
• Last Update Posted: Oct 19, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Gradalis, Inc.: Papillary Serous Ovarian Cancer; Endometrioid Ovarian Cancer; Epithelial Ovarian Cancer
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Bevacizumab; Vaccines

Study Results

Participant Flow

Recruitment Details	This study recruited subjects from CL-PTL-105 who recurred and were either randomized to the control/observation arm (Group B) or screen-failed but had successful manufacturing of Vigil (minimum of 4 doses).
Pre-assignment Detail	5 subjects were enrolled and started Vigil treatment plus Bevacizumab. 2 subjects completed treatment and 3 did not complete treatment due to disease progression (2) and withdrawal of consent (1).

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Period Title: Overall Study
STARTED	5
COMPLETED	2
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Overall Participants	5
Age, Customized (Count of Participants)
0-15 Years	0 0%
16-64 Years	3 60%
65 Years and Older	2 40%
Sex: Female, Male (Count of Participants)
Female	5 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	5 100%
Black/African American	0 0%
Asian	0 0%
Hispanic	0 0%
Other	0 0%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

5 subjects were enrolled and started Vigil treatment. 2 subjects completed treatment and 3 did not complete treatment due to disease progression (2) and withdrawal of consent (1). There is no Outcome Measure Data table because Time to Progression (TTP) and Response Rate (RR) were not collected and analyzed. This study was terminated.

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Measure Participants	0

2. Primary Outcome

Title	Response Rate
Description	Response will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

5 subjects were enrolled and started Vigil treatment. 2 subjects completed treatment and 3 did not complete treatment due to disease progression (2) and withdrawal of consent (1). There is no Outcome Measure Data table because Time to Progression (TTP) and Response Rate (RR) were not collected and analyzed. This study was terminated.

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Measure Participants	0

3. Secondary Outcome

Title	Number of Alive Subjects
Description	Survival status of patients after treatment was determined by following these patients up to 24 months.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

5 subjects were enrolled and started Vigil treatment. 2 subjects completed treatment and 3 did not complete treatment due to disease progression (2) and withdrawal of consent (1). After 24 months, only 1 of the 5 subjects was alive. Statistical analysis was not done. This study was terminated.

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Measure Participants	5
Alive Subjects After 24 months	1 20%
Dead Subjects After 24 months	4 80%

4. Secondary Outcome

Title	Enzyme-Linked ImmunoSorbent Spot (ELISPOT)
Description	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.
Time Frame	Baseline, End of Treatment (30 days after last dose) up to 12 months

Outcome Measure Data

Analysis Population Description

5 subjects were enrolled and started Vigil treatment. 2 subjects completed treatment and 3 did not complete treatment due to disease progression (2) and withdrawal of consent (1). After 12 months, all 5 subjects had positive ELISPOT response. Statistical analysis was not done. This study was terminated.

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Measure Participants	5
ELISPOT-Positive After 12 months	5 100%
ELISPOT-Negative After 12 months	0 0%

Adverse Events

Arm/Group Title	Vigil™ Vaccine
Arm/Group Description	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). 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). Bevacizumab: Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
All Cause Mortality
	Vigil™ Vaccine
	Affected / at Risk (%)	# Events
Total	4/5 (80%)
Serious Adverse Events
	Vigil™ Vaccine
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
Hepatobiliary disorders
Acute Cholecystitis	1/5 (20%)	1
Infections and infestations
Pharyngitis	1/5 (20%)	1
Nervous system disorders
Intracerebral Hemorrhage	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Vigil™ Vaccine
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
General disorders
Injection Site Reaction	2/5 (40%)	33

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.