Salvage Ovarian FANG™ Vaccine + Carboplatinum

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1
• 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 or patients with vaccine prepared for CL-PTL 105 but did not otherwise qualify.
3. 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.
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
8. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.
9. 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. Patient must not have received any other investigational agents within 4 weeks prior to study entry.
3. Patients who require parenteral hydration of nutrition and have evidence of partial bowel obstruction or perforation.
4. Patients with history of brain metastases.
5. Patients with compromised pulmonary disease.
6. 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.
7. Prior splenectomy.
8. Prior malignancy (excluding nonmelanoma carcinomas of the skin and carcinoma in situ cervix) unless in remission for ≥ 2 years.
9. Kaposi's Sarcoma.
10. Patients with peripheral neuropathy ≥2 (paclitaxel).
11. Uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
12. Patients with known HIV.
13. Patients with chronic Hepatitis B and C infection.
14. 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 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; Patients meeting eligibility criteria will receive Vigil™ 1.0 x 10e7 cells/intradermal injection once every 3 weeks.; Other Names: formerly known as FANG™; bi-shRNA furin and GMCSF Augmented Autologous Tumor Cell Vaccine; Drug: Carboplatinum; 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.; Drug: Carboplatinum and Taxol; 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Alive Subjects	Survival status of patients after treatment will be determined.	24 months

Collaborators and Investigators

• Sponsor: Gradalis, Inc.
• Investigators: Principal Investigator: Minal Barve, MD, Principal Investigator

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: June 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 8, 2016

Study Registration Dates

• First Submitted: May 29, 2013
• First Submitted That Met QC Criteria: May 29, 2013
• First Posted (Estimate): June 3, 2013

Study Record Updates

• Last Update Posted (Actual): June 19, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: 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; Carboplatin; Vaccines
• Other Study ID Numbers: CL-PTL 110