Salvage Ovarian FANG™ Vaccine + Carboplatinum

Study Overview
=================
Brief Summary
-----------------
This is a Phase II study of Vigil™ autologous tumor cell vaccine integrated with carboplatinum. All patients will have Vigil™ prepared and stored from ovarian tumor cells obtained at the time of primary surgical debulking. Patients meeting eligibility criteria will receive either carboplatinum alone (AUC 6/30 minute infusion) or carboplatinum (AUC 5/30 minute infusion) and taxol (175 mg/m2/3 hour infusion) one day prior to Vigil™ 1.0 x 10e7 cells/intradermal injection, once every 3 weeks.

Official Title
-----------------
Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) Integrated With Chemotherapy for Patients With Recurrent Cisplatinum Sensitive Ovarian Cancer Participating in Study CL-PTL 105

Conditions
-----------------
Stage III Ovarian Cancer, Stage IV Ovarian Cancer

Intervention / Treatment
-----------------
* Biological: Vigil™ Vaccine
* Drug: Carboplatinum
* Drug: Carboplatinum and Taxol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed papillary serous or endometrioid ovarian cancer. Previous randomization to Gradalis, Inc. protocol CL-PTL 105; observation arm (Group B) or or patients with vaccine prepared for CL-PTL 105 but did not otherwise qualify. Recurrent cisplatinum-sensitive 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 after a 6 month period after platinum treatment. 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: Absolute granulocyte count ≥ 1,500/mm3 Absolute lymphocyte count ≥ 200/mm3 Platelets ≥ 100,000/mm3 Total bilirubin ≤ 1.5 x ULN AST(SGOT)/ALT(SGPT)/alkaline phosphatase ≤ 2.5 x ULN Creatinine < 1.5 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. 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 peripheral neuropathy ≥2 (paclitaxel). 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vigil™ Vaccine<br>Patients meeting eligibility criteria will receive either carboplatinum alone (AUC 6/30 minute infusion) or carboplatinum (AUC 5/30 minute infusion) and taxol (175 mg/m2 3-hour infusion) one day prior to Vigil™ 1.0 x 10e7 cells/ intradermal injection, once every three weeks. At recurrence, patients allergic to carboplatinum will receive docetaxel 75 mg/m2/1 hour infusion, one day prior to Vigil™ 1.0 x 10e7 cells/intradermal injection every 3 weeks. Patients with stable disease (SD) or better and unable to tolerate continued chemotherapy will be allowed to continue Vigil™ alone for up to 12 cycles or as long as vaccine is available; conversely, patients with SD or better who exhaust Vigil™ supply may continue on chemotherapy alone. | Biological: Vigil™ Vaccine<br>* Patients meeting eligibility criteria will receive Vigil™ 1.0 x 10e7 cells/intradermal injection once every 3 weeks.<br>* Other names: formerly known as FANG™;Drug: Carboplatinum<br>* Patients meeting eligibility criteria will receive either carboplatinum alone (AUC 6/30 minute infusion) or carboplatinum (AUC 5/30 minute infusion) and taxol (175 mg/m2 3-hour infusion) one day prior to Vigil™ 1.0 x 10e7 cells/ intradermal injection, once every three weeks. At recurrence, patients allergic to carboplatinum will receive docetaxel 75 mg/m2/1 hour infusion, one day prior to Vigil™ 1.0 x 10e7 cells/intradermal injection every 3 weeks. Patients with stable disease (SD) or better and unable to tolerate continued chemotherapy will be allowed to continue Vigil™ alone for up to 12 cycles or as long as vaccine is available; conversely, patients with SD or better who exhaust Vigil™ supply may continue on chemotherapy alone.<br>Drug: Carboplatinum and Taxol<br>* Patients meeting eligibility criteria will receive either carboplatinum alone (AUC 6/30 minute infusion) or carboplatinum (AUC 5/30 minute infusion) and taxol (175 mg/m2 3-hour infusion one day prior to Vigil™ 1.0 x 10e7 cells/ intradermal injection, once every three weeks. At recurrence, patients allergic to carboplatinum will receive docetaxel 75 mg/m2/1 hour infusion, one day prior to Vigil™ 1.0 x 10e7 cells/intradermal injection every 3 weeks. Patients with stable disease (SD) or better and unable to tolerate continued chemotherapy will be allowed to continue Vigil™ alone for up to 12 cycles or as long as vaccine is available; conversely, patients with SD or better who exhaust Vigil™ supply may continue on chemotherapy alone.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | Time to progression (TTP) will be determined following Carboplatinum 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 | 
| Response Rate | Response will be evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Analysis in Blood | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian cancer