Sarcoma, Ewing
Conditions
Keywords
Relapsed and refractory Ewing's Sarcoma
Brief summary
This study is a multicenter, single-arm, open-label Phase II clinical trial evaluating TK216 in combination with vincristine in the treatment of relapsed or refractory Ewing sarcoma (ES) including Ewing's sarcoma family tumors (ESFTs).
Detailed description
Ewing sarcoma is characterized by genomic rearrangements resulting in over-expression of ets family transcription factors driving tumor progression. TK216 is designed to inhibit this effect by inhibiting downstream effects of the EWS-FLI1 transcription factor. Based on USA RP2D result, designed as a single arm, multicenter open-label study，this study is the first study of TK216 in Chinese subjects with Ewing sarcoma. The study is designed to establish safety and efficacy data in combination with vincristine to assess the potential of TK216 for further development.
Interventions
BIOLOGICALTK216+Vincristin
TK216 was continuously administered for 14 days，then rest for 14 days. Vincristin is given before TK216 only in the first day of each cycle, the first cycle of VCR is 0.75mg/m\^2 and 1.5mg/m\^2 from the second cycle，every 28 days is a study cycle.
Sponsors
Shanghai Pharmaceuticals Holding Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following inclusion criteria to be eligible for this study: 1. Willing to sign the informed consent form. 2. Participants with relapsed or refractory ES (including ESFT, except Ewing-like sarcoma) confirmed by cytohistology or molecular biology. 3. Life expectancy of at least 3 months. 4. Participants age ≥ 14 years, regardless of gender. 5. At least one measurable lesion according to RECIST version 1.1. 6. Agree to have a central venous catheter in place prior to initiating infusion of study drug. 7. Prior radiotherapy is allowed if ≥ 2 weeks must have elapsed for local palliative external beam radiotherapy; ≥ 6 months must have elapsed if systemic radiotherapy, external craniospinal irradiation or \> 50% pelvic radiotherapy; and ≥ 6 weeks must have elapsed for other substantial bone marrow radiotherapy before the first dose. Participants who have received brain radiotherapy must have completed whole brain radiotherapy and/or gamma knife surgery at least 4 weeks prior to enrollment. 8. Stem Cell Transplant or Rescue without TBI：no evidence of active graft-versus-host disease and ≥ 3 months must have elapsed since transplant. 9. Symptomatic CNS metastases must have been treated and remain stable for at least 4 weeks prior to the first dose of the study drug, or patients with asymptomatic brain metastases. 10. Adequate hematological and organ functions fulfilling the following laboratory requirements, and these results should be obtained within 7 days prior to the first dose: 11. ECOG performance score 0-2. 12. Cardiac ejection fraction ≥ 50% or shortening fraction ≥ 28%. 13. Eligible male and female participants of childbearing potential must consent to use reliable methods of contraception with their partners for at least 4 weeks before the start of protocol therapy, for the duration of study participation, and for at least 6 months after the last dose. Women of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first dose. 14. Without any contraindication to vincristine.
Exclusion criteria
Participants will not be enrolled if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (IRC) | Up to 2 years after TK216 introduction | Determination of the Objective Response Rate of all patients by IRC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Investigator) | Up to 2 years after TK216 introduction | Determination of the Objective Response Rate of all patients by investigators |
| Progression-free survival (PFS) | Up to 2 years after TK216 introduction | Determination of the progression-free survival of all patients |
| Overall survival (OS) | Up to 2 years after TK216 introduction | Determination of the overall survival times of all patients |
| Disease control rate (DCR) | Up to 2 years after TK216 introduction | Determination of the disease control rate of all patients |
| Duration of remission (DOR) | Up to 2 years after TK216 introduction | Determination of the duration of remission of all patients |
| Drug concentration in plasma | Up to 2 years after TK216 introduction | Determination of drug concentration in plasma of all patients |
| Number of patients with adverse events | Up to 2 years after TK216 introduction | Adverse event type, incidence, duration, correlation with study drug |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYang Yao
Shanghai 6th People's Hospital
Outcome results
None listed