Trials / Completed

CompletedNCT02736565

Pbi-shRNA™ EWS/FLI1 Type 1 LPX in Subjects With Advanced Ewing's Sarcoma

Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 7 (actual)

Sponsor: Gradalis, Inc. · Industry
Sex: All
Age: 8 Years
Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the safety and the maximum tolerated dose of of pbi-shRNA™ EWS/FLI1 Type 1 lipoplex in patients with advanced Ewing's sarcoma.

Detailed description

Eligible participants with advanced Ewing's sarcoma will be accrued in 3-subject dose escalation cohorts using the following escalation schema (50%→33%→25%→25%→25%) at a starting IV dose of 0.04 mg/kg and up to a dose of 0.156mg/kg. For this first in class study of pbi-shRNA™ EWS/FLI1 Type 1 lipoplex, Dose Limiting Toxicity (DLT) will be defined as any ≥ Grade 3 toxicity reported within the four weeks following the first administration of the investigational product, regardless of attribution. Any other ≥ Grade 3 toxicity encountered after the first four weeks post Dose 1 on Cycle 1 will be reported according to the CTCAE Version 4.0 but not defined as DLTs. If 1 of 3 subjects within a dose cohort experiences a DLT, that dose cohort will be expanded to six subjects provided no further subjects experience a DLT. If no further subjects experience a DLT, dose-escalation may continue. If ≥2 subjects within a dose cohort experiences a DLT, this will define the DLT dose level and the Maximum Tolerated Dose (MTD) will have been exceeded. The preceding dose level will be expanded to a total of 6 subjects and, if ≤1 subject experiences a DLT, that dose level will be considered the MTD. If no further subjects experience a DLT, dose-escalation may resume per escalation schema. Once the presumptive MTD is reached, an additional 6 subjects will be treated at that dose, designated the expanded MTD dose cohort. Participants who experience an unrelated Grade ≥3 toxicity that normalizes within 1 week may continue study treatment when the adverse event returns to Grade 1 or better at 50% of their assigned cohort dose. Delay in dosing of \>24 hours will require that the next dose is skipped. As of protocol Amendment No. 5, two subjects met the definition of dose limiting toxicity at Cohort 1, 0.04mg/kg, therefore the dose reduced by 50% and subsequent lipoplex administrations were given at 0.02mg/kg. Administration of 0.02mg/kg is defined as Cohort -1. An additional 6 subjects will be treated at Cohort -1, designated the expanded MTD dose cohort. If no further subjects experience a DLT at Cohort -1, dose re-escalation may continue to Cohort 0. The dose administered for subjects in Cohort 0 is 0.03mg/kg and would be defined as the optimal dose. All study agent administrations will cease for the occurrence of any of the following events at any time point over the four weeks following the first study agent dose administration to a participant: death, hospitalization for reasons other than those related to the participant's malignancy (excluding preplanned hospitalization and/or hospitalization for observation during the participant's first infusion), or any Grade ≥3 liver toxicity or Grade ≥4 pulmonary toxicity. All Grade ≥3 liver toxicities or Grade ≥4 pulmonary toxicities will be considered Adverse Events of Special Interest (AESI). Participants will receive an intravenous infusion twice a week for 4 weeks for a total of 8 infusions per cycle followed by 2 weeks of rest. Treatment with investigational product may continue as long as there is clinical benefit, no evidence of disease progression, and no other withdrawal criteria are met. Safety assessments will include physical examinations, performance status, laboratory assessments, and vital signs. Toxicity (Adverse Events) will be recorded for the duration of the participant's study treatment (following the first dose), and for up to 60 days following the last study treatment. Toxicities and AEs will be graded and reported using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.0. Efficacy assessments (response and progression) will be evaluated by local investigators using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex	Lipoplex is given intravenously as a single administration twice a week for 4 weeks for a total of 8 infusions per cycle followed by 2 weeks of rest. Treatment may continue as long as there is clinical benefit, no evidence of disease progression, and no other withdrawal criteria are met. First dose started on Cycle 1 Week 1 Day 1 followed by observation and safety assessment for 13 days. If no toxicity was observed, then another single administration of study agent was given at Cycle 1 Week 3 Day 1 followed by observation and safety for 6 days. If no toxicity was observed, then study agent was given twice a week on Days 1 and 4 over 3 weeks, for a total of 8 infusions per cycle, followed by a 2-week washout before starting each subsequent cycle. Cycle 1 = 8 weeks. Each subsequent cycles = 6 weeks.

Timeline

Start date: 2016-10-01
Primary completion: 2019-08-12
Completion: 2020-08-04
First posted: 2016-04-13
Last updated: 2023-11-13

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02736565. Inclusion in this directory is not an endorsement.