A Clinical Study of TK216 in Patients With Relapsed or Refractory Ewing's Sarcoma

Sponsor
Shanghai Pharmaceuticals Holding Co., Ltd (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05046314
Collaborator
(none)
30
8
1
16
3.8
0.2

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Biological: TK216+Vincristin
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Efficacy and Safety of TK216 in Subjects With Relapsed or Refractory Ewing's Sarcoma:a Phase II Clinical Trial in China
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Sep 13, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: TK216+Vincristin

Biological: TK216+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.

Outcome Measures

Primary Outcome Measures

  1. Objective Response Rate (IRC) [Up to 2 years after TK216 introduction]

    Determination of the Objective Response Rate of all patients by IRC

Secondary Outcome Measures

  1. Objective Response Rate (Investigator) [Up to 2 years after TK216 introduction]

    Determination of the Objective Response Rate of all patients by investigators

  2. Progression-free survival (PFS) [Up to 2 years after TK216 introduction]

    Determination of the progression-free survival of all patients

  3. Overall survival (OS) [Up to 2 years after TK216 introduction]

    Determination of the overall survival times of all patients

  4. Disease control rate (DCR) [Up to 2 years after TK216 introduction]

    Determination of the disease control rate of all patients

  5. Duration of remission (DOR) [Up to 2 years after TK216 introduction]

    Determination of the duration of remission of all patients

  6. Drug concentration in plasma [Up to 2 years after TK216 introduction]

    Determination of drug concentration in plasma of all patients

  7. Number of patients with adverse events [Up to 2 years after TK216 introduction]

    Adverse event type, incidence, duration, correlation with study drug

Eligibility Criteria

Criteria

Ages Eligible for Study:
14 Years and Older
Sexes Eligible for Study:
All
Accepts 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 exclusion criteria:
  1. Current participation in another therapeutic clinical trial.

  2. Having received anti-tumor chemotherapy, targeted therapy or immunotherapy within 4 weeks prior to the first dose; having received Chinese herbal medicine or Chinese patent medicine-based therapies with definite anti-tumor indications within 3 weeks before study drug usage.

  3. Having received systemic corticosteroids or other systemic immunosuppressive agents within 14 days prior to study, with the following exceptions:

  4. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption;

  5. Short-term (≤ 7 days), prophylactic use of corticosteroids or for the treatment of non-autoimmune diseases

  6. Unresolved, > Grade 1 toxicity related to prior anti-tumor therapy prior to the study, according to the CTCAE version 5.0.

  7. History of previous cancer, except squamous cell or basal -cell carcinoma of the skin or any in situ carcinoma that has been completely resected, which required therapy within the previous 3 years.

  8. Any of the following within 6 months: uncontrolled congestive heart failure (NYHA III-IV); uncontrolled angina; onset of cerebrovascular event or transient ischemic attack; pulmonary embolism; deep vein thrombosis and symptomatic bradycardia that require the use of antiarrhythmic drugs.

  9. History of QTc prolongation

  10. History of additional risk factors for torsades de pointes

  11. Use of concomitant medications that may increase or possibly increase the risk to prolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia.

  12. Having received surgical therapies (except diagnostic surgery, such as tumor biopsy, diagnostic puncture, etc.), including surgical and interventional therapies, within 4 weeks prior to treatment.

  13. Systemic use of antibiotics for ≥ 7 days within 4 weeks before TK216 treatment, or have fever of unknown origin (> 38.5 °C)

  14. Positive test results for hepatitis B surface antigen, hepatitis C antibody and HIV antibody during screening.

  15. Females who are pregnant or lactating.

  16. Have taken potent inducers or inhibitors of CYP3A4, potent inhibitors of CYP2C19 within 2 weeks prior to the first dose of study drug, or substrates of CYP3A4/CPY2C19 with a narrow therapeutic window.

  17. Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risk associated with study participation or study drug management, or may interfere with the interpretation of the study results.

  18. Participants who are not suitable for participating in this study due to any reason as judged by the investigator.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Peking University People's Hospital Beijing Beijing China 100044
2 Henan Cancer Hospital Zhengzhou Henan China 450003
3 Henan Provincial People's Hospital Zhengzhou Henan China 450003
4 Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China 100005
5 Hunan Cancer Hospital Changsha Hunan China 410031
6 Shanghai Sixth People's Hospital Shanghai Shanghai China 200233
7 Tianjin Medical University Cancer Institude & Hospital Tianjin Tianjin China 300060
8 The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China 310003

Sponsors and Collaborators

  • Shanghai Pharmaceuticals Holding Co., Ltd

Investigators

  • Principal Investigator: Yang Yao, Shanghai 6th People's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shanghai Pharmaceuticals Holding Co., Ltd
ClinicalTrials.gov Identifier:
NCT05046314
Other Study ID Numbers:
  • TK216-001
First Posted:
Sep 16, 2021
Last Update Posted:
Jul 26, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Shanghai Pharmaceuticals Holding Co., Ltd
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 26, 2022