Stage III Ovarian Cancer, Stage IV Ovarian Cancer
Conditions
Keywords
Papillary Serous Ovarian Cancer, Endometrioid Ovarian Cancer, Epithelial Ovarian Cancer
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.
Interventions
BIOLOGICALVigil™ 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).
DRUGBevacizumab
Patients meeting eligibility criteria will receive bevacizumab 10 mg/kg intravenously every 2 weeks.
Sponsors
Gradalis, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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: 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. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Vigil™ Vaccine |
|---|---|
| Age, Customized Age 0-15 Years | 0 Participants |
| Age, Customized Age 16-64 Years | 3 Participants |
| Age, Customized Age 65 Years and Older | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 5 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 5 |
| other Total, other adverse events | 2 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Response Rate
Response will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline.
Time frame: Up to 12 months
Population: 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.
Primary
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.
Time frame: 24 months
Population: 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.
Secondary
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.
Time frame: Baseline, End of Treatment (30 days after last dose) up to 12 months
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | ELISPOT-Positive After 12 months | 5 Participants |
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | ELISPOT-Negative After 12 months | 0 Participants |
Secondary
Number of Alive Subjects
Survival status of patients after treatment was determined by following these patients up to 24 months.
Time frame: 24 months
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vigil™ Vaccine | Number of Alive Subjects | Alive Subjects After 24 months | 1 Participants |
| Vigil™ Vaccine | Number of Alive Subjects | Dead Subjects After 24 months | 4 Participants |