Pbi-shRNA™ EWS/FLI1 Type 1 LPX in Subjects With Advanced Ewing's Sarcoma
Ewing's sarcoma characterized by the t(11; 22) (q24; q12) translocation at several but prioritized breakpoint sites, resulting in the EWS/FLI1 fusion gene is the second most frequently diagnosed primary malignant bone tumor in the US with an annual incidence, from birth to age 20, of 2.9 cases per million population. The survival rate for patients with high-risk recurrent disease (relapse < 2 years) is < 10% at 5 years. Moreover, of patients who progress after second line treatment, eighty percent do not achieve a second complete response and of these patients < 10% survive one year. Refractory patients to both frontline and second line therapy have even worse prognosis.
The EWS/FLI1 gene is well known as the driver gene of Ewing's sarcoma. We designed a novel pbi-shRNA™ EWS/FLI1 Type 1 LPX which has demonstrated sufficient specificity, safety and efficacy in animal testing to justify Phase I testing. Clinical safety (no ≥ grade 3 product related toxic effect) and target specific activity has been observed with other bi-shRNA products involving 147 cancer patients (698 separate dose administrations) (BB-IND 14205; BB-IND 14938). Moreover, safety has been observed with IV delivery of pbi-shRNA™ EWS/FLI1 Type 1 LPX in murine and swine testing via multidose IV administration.
Study testing of pbi-shRNA™ EWS/FLI1 Type 1 LPX will involve patients (≥age 8) with advanced Ewing's sarcoma. The first 3 subjects enrolled onto the study as well as the first subject enrolled into each dose cohort must be 16 years of age or older. pbi-shRNA™ EWS/FLI1 Type 1 LPX will be given via intravenous infusion twice a week for 4 weeks (e.g. Mon and Thurs, preferred) for a total of 8 infusions of the product per cycle followed by a 2 week washout period. Patients will be accrued in 3-patient dose escalation cohorts using the following escalation schema (50% to 33% to 25% to 25% to 25%) at a starting IV dose of 0.04 mg/kg.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma|
- Safety: adverse events as assessed by CTCAE v4.0 [ Time Frame: 1 year ]
- Efficacy measured by Clinical Response [ Time Frame: 1 year ]Disease Response
|Study Start Date:||October 2016|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: pbi-shRNA™ EWS/FLI1 Type 1 LPX
Subjects will accrue in 3 to 6-subject escalation cohorts up to a dose of 0.156mg/kg of DNA / single dose.
An intravenous infusion will be administered twice a week for 4 weeks (e.g. Mon and Thurs, preferred) for a total of 8 infusions of the product 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.
Biological: pbi-shRNA™ EWS/FLI1 Type 1 LPX
Other Name: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex
Please refer to this study by its ClinicalTrials.gov identifier: NCT02736565
|Contact: Gladice Wallravenfirstname.lastname@example.org|
|United States, Texas|
|Mary Crowley Cancer Research Centers||Recruiting|
|Dallas, Texas, United States, 75230|
|Contact: Referral Office 972-566-3000 email@example.com|
|Principal Investigator: Maurizio Ghisoli, MD|
|Study Director:||John Nemunaitis, MD||Strike Bio, Inc.|