Ewing's SarcomaPhase 1NCT02736565
Pbi-shRNA™ EWS/FLI1 Type 1 LPX in Subjects With Advanced Ewing's Sarcoma
A Phase 1 study testing pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex in people with Ewing's Sarcoma and Ewing Family of Tumors, run by Gradalis, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Ewing's Sarcoma, Ewing Family of Tumors, Ewing's Tumor Metastatic
- What is being tested?
- pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to 4 Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).
- Age ≥8 years.
- Evidence of EWS translocation fusion by FISH or RT-PCR or NGS.
- Evidence of Type 1 fusion by molecular diagnostics.
- Refractory or intolerant to standard of care. Subjects must have failed surgery (if resectable), radiation (if no function-preserving surgical approach at primary site, unresectable primary following induction chemotherapy, residual microscopic or gross disease after surgery or inadequate margins), and the following chemotherapy agents: doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide.
- ECOG performance status (PS) = 0-2, or Karnofsky PS ≥60% or Lansky PS ≥60%.
Show all 13Show fewer
- Normal organ and marrow function as defined below:
- Absolute granulocyte count ≥1,000/mm3 Absolute lymphocyte count ≥400/mm3 Platelets ≥100,000/mm3 Total bilirubin ≤ institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal Creatinine <1.5 mg/dL
- Normal pulmonary function as defined as FEV1/FVC greater than 70% in adults or greater than 80% in individuals between 8 and 18 years of age.
- Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
- If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.
- Ability to understand and the willingness to sign a written informed protocol specific consent. Pediatric patients must sign an assent with a parent or legal guardian sign a written informed consent, per institutional guidelines.
- Subjects will NOT be eligible for study registration and enrollment if meeting any of the following criteria:
Who cannot join
- Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first infusion.
- Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
- Patients with PET avid disease only will be excluded.
- Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
- History of or current evidence of thrombosis.
- History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the Investigator.
Show all 9Show fewer
- Known HIV or chronic Hepatitis B or C infection.
- Have signs and symptoms consistent with an active infection.
- Live vaccination for the prevention of infectious disease administered <30 days prior to the start of study therapy or inactivated vaccination <14 days prior to the start of study therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma
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.
Read the 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
- Ewing's Sarcoma, Ewing Family of Tumors, Ewing's Tumor Metastatic, Ewing's Sarcoma Metastatic, Ewing's Tumor Recurrent, Rare Diseases
- Being tested
- pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex
- Keywords
- bone cancer, EWS gene, neuroectodermal tumor, pNET, sarcoma, soft tissue, ESFT, Immunotherapy
- Medical subject headings
- Sarcoma, Ewing, Neuroectodermal Tumors, Primitive, Peripheral, Rare Diseases, Sarcoma, Bone Neoplasms, Neuroectodermal Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pbi-shRNA™ EWS/FLI1 Type 1 LipoplexBiological
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort -1 | Experimental | 0.02mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 0 | Experimental | 0.03mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 1 | Experimental | 0.04mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 2 | Experimental | 0.06mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 3 | Experimental | 0.08mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 4 | Experimental | 0.10mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 5 | Experimental | 0.125mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
| Cohort 6 | Experimental | 0.156mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex Receives: Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Adverse events(AEs) will be recorded for the duration of the participant's study treatment (following the first dose of the investigational product), and for up to 60 days following the last study treatment. AEs will be graded and reported using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. The relationship of each event to the investigational product will be assessed by the Treating Physician.
Measured: From first dose and up to 60 days following the last treatment, up to approximately 13 months.
Determine the maximum tolerated dose of intravenous administration of lipoplex
By observing the Dose Limiting Toxicities, including ≥ Grade 3 toxicity encountered within the four weeks following the first administration of the investigational product the MTD will be determined.
Measured: From first subject, first dose and after an additional 6 subjects have been treated at the MTD, up to 4 weeks.
Secondary outcomes (3)
To assess disease response for different cohorts following pbi-shRNA™ EWS/FLI1 Type 1 lipoplex administration at different dose(s).
Radiological assessment of tumors, chest, abdomen, and pelvis to include, at a minimum, CT (or MRI), used to evaluate measurable or non-measurable disease. To be obtained at baseline and quarterly thereafter (+/- 4 weeks) until progressive disease is noted. For those subjects with CT or MRI evidence of response following the administration of the study agent, a confirmatory scan will be performed one month later.
Measured: From Baseline and quarterly thereafter until progressive disease is noted, up to approximately 12 months.
To assess the pharmacokinetics of pbi-shRNA™ EWS/FLI1 Type 1 plasmid.
Serum for pharmacokinetics (PK) analysis will be collected on Cycle 1 Week 1 Day 1, Cycle 1 Week 6 Day 4, and Cycle 2 Week 1 Day 1 at the following time points (±10%): 30 minutes prior to study agent administration and at the following time points after the initiation of study agent administration: 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours.
Measured: From Cycle 1 Week 1 Day 1 and until Cycle 2 Week 1 Day 1, approximately 8 weeks.
To assess ctDNA (EWSR-FLI1) levels and compare to tumor burden and disease response prior to and following pbi-shRNA™ EWS/FLI1 Type 1 lipoplex administration.
Blood for circulating tumor DNA analysis will be collected at Cycle 1 Week 1 Day 1, Cycle 1 Week 3 Day 1, Cycle 2 Week 1 Day 1 prior to product infusion and every even cycle thereafter at Week 1 Day 1 prior to product infusion.
Measured: From Cycle 1 Week 1 Day 1 and until the last even cycle where product was administered, up to approximately 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study startOct 2016
- Primary completion12 Aug 2019
- Study completion4 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gradalis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Nemunaitis, MD, Study director, Gradalis, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02736565
- Sponsor's protocol ID
- CL-PTL-001
- Status last verified
- Nov 2023
- First submitted
- 4 Apr 2016
- Last updated
- 13 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barve M, Wang Z, Kumar P, Jay CM, Luo X, Bedell C, Mennel RG, Wallraven G, Brunicardi FC, Senzer N, Nemunaitis J, Rao DD. Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer. Mol Ther. 2015 Jun;23(6):1123-1130. doi: 10.1038/mt.2015.14. Epub 2015 Jan 26.
PubMed 25619726Wang Z, Rao DD, Senzer N, Nemunaitis J. RNA interference and cancer therapy. Pharm Res. 2011 Dec;28(12):2983-95. doi: 10.1007/s11095-011-0604-5. Epub 2011 Oct 19.
PubMed 22009588Senzer 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.
PubMed 22186789Rao DD, Jay C, Wang Z, Luo X, Kumar P, Eysenbach H, Ghisoli M, Senzer N, Nemunaitis J. Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1412-22. doi: 10.1038/mt.2016.93. Epub 2016 May 11.
PubMed 27166877
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma
- ClinicalTrials.gov ID
- NCT02736565
- Acronym / sponsor ID
- CL-PTL-001
- Conditions
- Ewing's Sarcoma, Ewing Family of Tumors, Ewing's Tumor Metastatic, Ewing's Sarcoma Metastatic, Ewing's Tumor Recurrent, Rare Diseases
- Keywords
- bone cancer, EWS gene, neuroectodermal tumor, pNET, sarcoma, soft tissue, ESFT, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Gradalis, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2016 (actual)
- Primary completion
- 12 Aug 2019 (actual)
- Study completion
- 4 Aug 2020 (actual)
- First posted
- 13 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort -1 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.02mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 0 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.03mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 1 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.04mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 2 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.06mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 3 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.08mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 4 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.10mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 5 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.125mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
| Cohort 6 | Experimental | Biological: pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex0.156mg/kg pbi-shRNA™ EWS/FL/I1 Type 1 Lipoplex |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).
- Age ≥8 years.
- Evidence of EWS translocation fusion by FISH or RT-PCR or NGS.
- Evidence of Type 1 fusion by molecular diagnostics.
- Refractory or intolerant to standard of care. Subjects must have failed surgery (if resectable), radiation (if no function-preserving surgical approach at primary site, unresectable primary following induction chemotherapy, residual microscopic or gross disease after surgery or inadequate margins), and the following chemotherapy agents: doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide.
Key exclusion criteria (9 listed)
- Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first infusion.
- Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
- Patients with PET avid disease only will be excluded.
- Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
- History of or current evidence of thrombosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pbi-shRNA™ EWS/FLI1 Type 1 LipoplexAlso: LipoplexLipoplex 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. | Biological | Cohort -1, Cohort 0, Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time frame: From first dose and up to 60 days following the last treatment, up to approximately 13 months.
Adverse events(AEs) will be recorded for the duration of the participant's study treatment (following the first dose of the investigational product), and for up to 60 days following the last study treatment. AEs will be graded and reported using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. The relationship of each event to the investigational product will be assessed by the Treating Physician.
Determine the maximum tolerated dose of intravenous administration of lipoplex
Time frame: From first subject, first dose and after an additional 6 subjects have been treated at the MTD, up to 4 weeks.
By observing the Dose Limiting Toxicities, including ≥ Grade 3 toxicity encountered within the four weeks following the first administration of the investigational product the MTD will be determined.
3 secondary outcomes
To assess disease response for different cohorts following pbi-shRNA™ EWS/FLI1 Type 1 lipoplex administration at different dose(s).
Time frame: From Baseline and quarterly thereafter until progressive disease is noted, up to approximately 12 months.
To assess the pharmacokinetics of pbi-shRNA™ EWS/FLI1 Type 1 plasmid.
Time frame: From Cycle 1 Week 1 Day 1 and until Cycle 2 Week 1 Day 1, approximately 8 weeks.
To assess ctDNA (EWSR-FLI1) levels and compare to tumor burden and disease response prior to and following pbi-shRNA™ EWS/FLI1 Type 1 lipoplex administration.
Time frame: From Cycle 1 Week 1 Day 1 and until the last even cycle where product was administered, up to approximately 1 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2023.
- Background: PubMed 25619726Barve M, Wang Z, Kumar P, Jay CM, Luo X, Bedell C, Mennel RG, Wallraven G, Brunicardi FC, Senzer N, Nemunaitis J, Rao DD. Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer. Mol Ther. 2015 Jun;23(6):1123-1130. doi: 10.1038/mt.2015.14. Epub 2015 Jan 26.
- Background: PubMed 22009588Wang Z, Rao DD, Senzer N, Nemunaitis J. RNA interference and cancer therapy. Pharm Res. 2011 Dec;28(12):2983-95. doi: 10.1007/s11095-011-0604-5. Epub 2011 Oct 19.
- Background: PubMed 22186789Senzer 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.
- Background: PubMed 27166877Rao DD, Jay C, Wang Z, Luo X, Kumar P, Eysenbach H, Ghisoli M, Senzer N, Nemunaitis J. Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1412-22. doi: 10.1038/mt.2016.93. Epub 2016 May 11.
- Individual participant dataSharing planned: No
Related trials for Ewing's Sarcoma
RecruitingPhase 1/2
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma
Not yet recruitingPhase 1
GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors
Neuroblastoma (NBL), Ewing Sarcoma
Not yet recruitingPhase 1/2
Combination Immunotherapy Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
RecruitingPhase 1
International Phase I Trial of Dinutuximab Beta With VDC/IE in GD2-Positive Ewing Sarkoma
High-risk GD2 Positive Ewing Sarkoma
Not yet recruitingPhase 1/2
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Nemunaitis, MD study director
Gradalis, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex in people with Ewing's Sarcoma and Ewing Family of Tumors, run by Gradalis, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 (time frame: From first dose and up to 60 days following the last treatment, up to approximately 13 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02736565, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023.