Salvage Ovarian FANG™ Vaccine + Bevacizumab

Phase 2

Completed

Conditions: Stage IV Ovarian Cancer
Stage III Ovarian Cancer

Interventions: Biological: Vigil™ Vaccine
Drug: Bevacizumab

Registration Number: NCT01551745

Lead Sponsor: Gradalis, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Histologically confirmed papillary serous or endometrioid ovarian cancer.
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.
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.
Successful manufacturing of 4 vials of Vigil™ vaccine.
Recovered from all clinically relevant toxicities related to prior therapies.
ECOG PS 0-2 prior to Vigil™ vaccine administration.
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
Baseline blood pressure must be under 140/90
Urine protein-to-creatinine ratio < 1.0 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 protocol specific consent.

Exclusion Criteria

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.
Major surgery within 6 weeks or minor surgery within 2 weeks of receiving bevacizumab.
Patient must not have received any other investigational agents within 4 weeks prior to study entry.
Patients who require parenteral hydration of nutrition and have evidence of partial bowel obstruction or perforation.
Patients with history of brain metastases.
Patients with compromised pulmonary disease.
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.
Prior splenectomy.
Prior malignancy (excluding nonmelanoma carcinomas of the skin and carcinoma in situ cervix) unless in remission for ≥ 2 years.
Kaposi's Sarcoma.
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.
History of Stroke/Transient Ischemic Attack
Use of bleeding diathesis
Use of anti-coagulants
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.
Uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
Patients with known HIV.
Patients with chronic Hepatitis B and C infection.
Patients with uncontrolled autoimmune diseases.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vigil™ Vaccine	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).
Vigil™ Vaccine	Bevacizumab	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).

Primary Outcome Measures

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

Secondary Outcome Measures

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