Sarcoma Clinical Trial
Official title:
Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma
Verified date | November 2023 |
Source | Gradalis, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 7 |
Est. completion date | August 4, 2020 |
Est. primary completion date | August 12, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 8 Years and older |
Eligibility | Subjects will be eligible for registration if they meet all of the following inclusion criteria: Inclusion Criteria: 1. Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT). 2. Age =8 years. 3. Evidence of EWS translocation fusion by FISH or RT-PCR or NGS. 4. Evidence of Type 1 fusion by molecular diagnostics. 5. 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. 6. ECOG performance status (PS) = 0-2, or Karnofsky PS =60% or Lansky PS =60%. 7. 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 8. 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. 9. 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. 10. 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. 11. 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: Exclusion Criteria: 1. Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first infusion. 2. 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. 3. Patients with PET avid disease only will be excluded. 4. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for = 2 months. 5. History of or current evidence of thrombosis. 6. 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. 7. Known HIV or chronic Hepatitis B or C infection. 8. Have signs and symptoms consistent with an active infection. 9. 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. |
Country | Name | City | State |
---|---|---|---|
United States | Mary Crowley Cancer Research Centers | Dallas | Texas |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Gradalis, Inc. |
United States,
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. — View Citation
Rao 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. — View Citation
Senzer 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. — View Citation
Wang 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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | From first dose and up to 60 days following the last treatment, up to approximately 13 months. | |
Primary | 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. | From first subject, first dose and after an additional 6 subjects have been treated at the MTD, up to 4 weeks. | |
Secondary | 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. | From Baseline and quarterly thereafter until progressive disease is noted, up to approximately 12 months. | |
Secondary | 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. | From Cycle 1 Week 1 Day 1 and until Cycle 2 Week 1 Day 1, approximately 8 weeks. | |
Secondary | 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. | From Cycle 1 Week 1 Day 1 and until the last even cycle where product was administered, up to approximately 1 year. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04986748 -
Using QPOP to Predict Treatment for Sarcomas and Melanomas
|
||
Recruiting |
NCT04457258 -
68Ga-FAPi-46 PET/CT Scan in Imaging Patients With Sarcoma
|
Early Phase 1 | |
Completed |
NCT04474678 -
Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!")
|
N/A | |
Recruiting |
NCT05415098 -
Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Recruiting |
NCT04535713 -
GALLANT: Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma
|
Phase 2 | |
Completed |
NCT03521531 -
Burden and Medical Care of Sarcoma in Germany
|
||
Completed |
NCT02496520 -
Dendritic Cell-based Immunotherapy for Advanced Solid Tumours of Children and Young Adults
|
Phase 1/Phase 2 | |
Terminated |
NCT02054104 -
Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum
|
Phase 1/Phase 2 | |
Terminated |
NCT00788125 -
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04577014 -
Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Completed |
NCT04052334 -
Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma
|
Phase 1 | |
Completed |
NCT01593748 -
A Phase II Trial Comparing Gemcitabine and Pazopanib Versus Gemcitabine and Docetaxel for Patients With Advanced Soft Tissue Sarcoma
|
Phase 2 | |
Completed |
NCT00199849 -
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine
|
Phase 1 | |
Recruiting |
NCT04367779 -
Research of Biomarkers of Response to Proton Beam Therapy in Pediatric and Adult Patients.
|
||
Completed |
NCT01879085 -
Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
|
Phase 1/Phase 2 | |
Recruiting |
NCT04553692 -
Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers
|
Phase 1 | |
Completed |
NCT01209598 -
PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
|
Phase 2 | |
Completed |
NCT04553471 -
Palliative Lattice Stereotactic Body Radiotherapy (SBRT) for Patients With Sarcoma, Thoracic, Abdominal, and Pelvic Cancers
|
N/A | |
Withdrawn |
NCT04906876 -
A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
|
Phase 2 |