Clinical Trial: A Two-part Phase IIb Trial of Vigil in Ewing's Sarcoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Two-part Phase IIb Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Ewing's Sarcoma

Brief Summary: Based on the limited accrual to Part 1 of this study, Gradalis is opening Part 2 of this clinical protocol to assess the safety of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide. Part 2 will be conducted at the same centers as Part 1, studying intradermal autologous Vigil cancer vaccine (1.0 x 10e7 cells/injection; minimum of 4 to a maximum of 12 administrations) in patients with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory or intolerant to at least 1 prior line of chemotherapy. Patients undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of investigational product. Patients meeting eligibility criteria including manufacture of a minimum of 4 immunotherapy doses of Vigil will be registered to receive: (i) oral temozolimidetemozolomide 100 mg/m2 daily (Days 1 - 5, total dose 500 mg/m2/cycle), (ii) irinotecan 50 mg/m2 daily (Days 1 - 5, total dose 250mg/m2/cycle), orally or irinotecan 20mg/m2 daily (Days 1 - 5, total dose 100mg/m2/cycle), intravenously (iii) peg-filgrastim 100μg/kg (Day 6) subcutaneously (optional and may be administered at home), and (iv) Vigil 1.0 x 10e7 cells/injection, intradermally on Day 15 and every 43 weeks thereafter. One cycle = 21 days.

Detailed Summary:

Part 1 Methodology:

This is a multicenter, 1:1 randomized Phase IIb study of intradermal autologous Vigil immunotherapy (1.0 x 10e7 cells/injection; minimum of 4 to a maximum of 12 administrations) versus gemcitabine / docetaxel in patients with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory or intolerant to at least 2 prior lines of chemotherapy. Patients undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of investigational product. Patients meeting eligibility criteria including manufacture of a minimum of 4 immunotherapy doses will be randomized to receive either (1) intradermal Vigil every 28 days for 4-12 administrations, or (2) gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days. The primary trial objective is to determine the overall survival of patients treated with Vigil versus gemcitabine/docetaxel. Randomization may occur as early as vaccine is released (typically 3 - 4 weeks following tumor procurement) but no later than 8 weeks following tumor procurement. Randomization of patients will be stratified by Karnofsky Performance Status (KPS) ≥ 80% vs < 80%.

Patients will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored monthly. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell response to autologous tumor antigens will be collected at tissue procurement, baseline, and prior to product administration at Cycles 2, 4, end of treatment, and every 6 months thereafter.

Part 2 Methodology:

Based on the limited accrual to Part 1 of this study, Gradalis is opening
Sponsor: Gradalis, Inc.

Current Primary Outcome: Adverse Events, Laboratory Assessments and Physical Examinations [ Time Frame: 36 weeks ]

Original Primary Outcome: 1-year survival rate [ Time Frame: 1 year ]

Current Secondary Outcome: γIFN ELISPOT conversion rate from Blood Collected [ Time Frame: 1 year ]

Original Secondary Outcome:

• Overall Survival [ Time Frame: 5 years ]
  To determine and compare the overall survival of patients with metastatic Ewing's sarcoma refractory or intolerant to ≥ 2 prior lines of systemic chemotherapy treated with Vigil™ immunotherapy vs. gemcitabine/docetaxel.
• γIFN ELISPOT conversion rate [ Time Frame: 1 year ]
  To determine the γIFN ELISPOT conversion rate of subjects treated with Vigil™ immunotherapy vs gemcitabine/docetaxel.

Information By: Gradalis, Inc.

Dates:
Date Received: July 28, 2015
Date Started: July 2015
Date Completion: December 2018
Last Updated: May 4, 2017
Last Verified: May 2017