Clinical Trials Directory

Trials / Terminated

TerminatedNCT03495921

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Combination With Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma

Status
Terminated
Phase
Phase 3
Study type
Interventional
Enrollment
32 (actual)
Sponsor
Gradalis, Inc. · Industry
Sex
All
Age
2 Years
Healthy volunteers
Not accepted

Summary

The goal of this clinical trial was to compare participants with first relapse or refractory Ewing's sarcoma when treated with investigational product (Vigil) in addition to the standard treatment of irinotecan and temozolomide compared to the standard treatment of irinotecan and temozolomide alone. The main question it aimed to answer is "Will participants who receive Vigil in addition to irinotecan and temozolomide have a prolonged time to progression and improved quality of life compared to the participants who receive irinotecan and temozolomide alone?".

Detailed description

This was a multicenter, Phase III study in participants with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants who agreed to participation had tumor tissue harvested from a scheduled standard surgical procedure (e.g., tumor biopsy or palliative resection). The tumor tissue removed was shipped to Gradalis, Inc. to attempt to manufacture the investigational product, Vigil. Subjects who met eligibility criteria including manufacture of a minimum of 4 doses of Vigil were randomized 1:1 to either Group A (Vigil + Irinotecan + Temozolomide (Tem/Iri)) or Group B (Irinotecan + Temozolomide). Screening for the main portion of the study occurred as early as one week but no later than 8 weeks following tumor procurement. Subjects received repeat cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study. Subjects randomized to Group A (Vigil + Tem/Iri) received up to 12 doses depending upon the quantity of Vigil manufactured from the surgical specimen. 1 cycle = 21 days. If irinotecan + temozolomide was administered beyond 12 cycles, it was administered off study. Subjects randomized to Group B (Tem/Iri) may have crossed over to receive single agent Vigil every 21 days following End of Treatment assessment and documented disease progression confirmed by central radiology vendor, for up to 12 doses of Vigil depending upon the quantity of Vigil manufactured. Participants were managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis was collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT. After progression, participants were contacted quarterly for documentation of post study therapies and survival status information.

Conditions

Interventions

TypeNameDescription
BIOLOGICALVigilVigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.
DRUGIrinotecanInjectable formulation of irinotecan was distributed from central supplier. 1 Cycle (5 doses of 50 mg/m2 per syringe) was drawn into provided oral syringes and dispenses to the subject with instructions to refrigerate until administration.
DRUGTemozolomideDose: 100 mg/m2 daily, oral Schedule: Days 1-5, every 21 days Administered at least 1 hour before Irinotecan.

Timeline

Start date
2018-08-21
Primary completion
2022-01-20
Completion
2022-01-20
First posted
2018-04-12
Last updated
2023-04-26
Results posted
2023-04-26

Locations

15 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03495921. Inclusion in this directory is not an endorsement.