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

Primary Purpose

Sarcoma, Ewing

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
TK216+Vincristin
Sponsored by
Shanghai Pharmaceuticals Holding Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma, Ewing focused on measuring Relapsed and refractory Ewing's Sarcoma

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

    1. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption;
    2. Short-term (≤ 7 days), prophylactic use of corticosteroids or for the treatment of non-autoimmune diseases
  4. Unresolved, > Grade 1 toxicity related to prior anti-tumor therapy prior to the study, according to the CTCAE version 5.0.
  5. 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.
  6. 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.
  7. History of QTc prolongation
  8. History of additional risk factors for torsades de pointes
  9. 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.
  10. 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.
  11. Systemic use of antibiotics for ≥ 7 days within 4 weeks before TK216 treatment, or have fever of unknown origin (> 38.5 °C)
  12. Positive test results for hepatitis B surface antigen, hepatitis C antibody and HIV antibody during screening.
  13. Females who are pregnant or lactating.
  14. 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.
  15. 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.
  16. Participants who are not suitable for participating in this study due to any reason as judged by the investigator.

Sites / Locations

  • Peking University People's Hospital
  • Henan Cancer Hospital
  • Henan Provincial People's Hospital
  • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Hunan Cancer Hospital
  • Shanghai Sixth People's Hospital
  • Tianjin Medical University Cancer Institude & Hospital
  • The Second Affiliated Hospital Zhejiang University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TK216+Vincristin

Arm Description

Outcomes

Primary Outcome Measures

Objective Response Rate (IRC)
Determination of the Objective Response Rate of all patients by IRC

Secondary Outcome Measures

Objective Response Rate (Investigator)
Determination of the Objective Response Rate of all patients by investigators
Progression-free survival (PFS)
Determination of the progression-free survival of all patients
Overall survival (OS)
Determination of the overall survival times of all patients
Disease control rate (DCR)
Determination of the disease control rate of all patients
Duration of remission (DOR)
Determination of the duration of remission of all patients
Drug concentration in plasma
Determination of drug concentration in plasma of all patients
Number of patients with adverse events
Adverse event type, incidence, duration, correlation with study drug

Full Information

First Posted
August 24, 2021
Last Updated
August 23, 2023
Sponsor
Shanghai Pharmaceuticals Holding Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05046314
Brief Title
A Clinical Study of TK216 in Patients With Relapsed or Refractory Ewing's Sarcoma
Official Title
The Efficacy and Safety of TK216 in Subjects With Relapsed or Refractory Ewing's Sarcoma:a Phase II Clinical Trial in China
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 28, 2023 (Anticipated)
Primary Completion Date
September 13, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Pharmaceuticals Holding Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Ewing
Keywords
Relapsed and refractory Ewing's Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TK216+Vincristin
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
TK216+Vincristin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate (IRC)
Description
Determination of the Objective Response Rate of all patients by IRC
Time Frame
Up to 2 years after TK216 introduction
Secondary Outcome Measure Information:
Title
Objective Response Rate (Investigator)
Description
Determination of the Objective Response Rate of all patients by investigators
Time Frame
Up to 2 years after TK216 introduction
Title
Progression-free survival (PFS)
Description
Determination of the progression-free survival of all patients
Time Frame
Up to 2 years after TK216 introduction
Title
Overall survival (OS)
Description
Determination of the overall survival times of all patients
Time Frame
Up to 2 years after TK216 introduction
Title
Disease control rate (DCR)
Description
Determination of the disease control rate of all patients
Time Frame
Up to 2 years after TK216 introduction
Title
Duration of remission (DOR)
Description
Determination of the duration of remission of all patients
Time Frame
Up to 2 years after TK216 introduction
Title
Drug concentration in plasma
Description
Determination of drug concentration in plasma of all patients
Time Frame
Up to 2 years after TK216 introduction
Title
Number of patients with adverse events
Description
Adverse event type, incidence, duration, correlation with study drug
Time Frame
Up to 2 years after TK216 introduction

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must meet all of the following inclusion criteria to be eligible for this study: Willing to sign the informed consent form. Participants with relapsed or refractory ES (including ESFT, except Ewing-like sarcoma) confirmed by cytohistology or molecular biology. Life expectancy of at least 3 months. Participants age ≥ 14 years, regardless of gender. At least one measurable lesion according to RECIST version 1.1. Agree to have a central venous catheter in place prior to initiating infusion of study drug. 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. Stem Cell Transplant or Rescue without TBI:no evidence of active graft-versus-host disease and ≥ 3 months must have elapsed since transplant. 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. Adequate hematological and organ functions fulfilling the following laboratory requirements, and these results should be obtained within 7 days prior to the first dose: ECOG performance score 0-2. Cardiac ejection fraction ≥ 50% or shortening fraction ≥ 28%. 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. Without any contraindication to vincristine. Exclusion Criteria: Participants will not be enrolled if they meet any of the following exclusion criteria: Current participation in another therapeutic clinical trial. 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. Having received systemic corticosteroids or other systemic immunosuppressive agents within 14 days prior to study, with the following exceptions: Topical, ocular, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption; Short-term (≤ 7 days), prophylactic use of corticosteroids or for the treatment of non-autoimmune diseases Unresolved, > Grade 1 toxicity related to prior anti-tumor therapy prior to the study, according to the CTCAE version 5.0. 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. 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. History of QTc prolongation History of additional risk factors for torsades de pointes 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. 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. Systemic use of antibiotics for ≥ 7 days within 4 weeks before TK216 treatment, or have fever of unknown origin (> 38.5 °C) Positive test results for hepatitis B surface antigen, hepatitis C antibody and HIV antibody during screening. Females who are pregnant or lactating. 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. 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. Participants who are not suitable for participating in this study due to any reason as judged by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Yao
Phone
13916138801
Email
yangyao_6@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Haiyan Hu
Phone
18930174575
Email
xurill04@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yang Yao
Organizational Affiliation
Shanghai 6th People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Guo
First Name & Middle Initial & Last Name & Degree
Jie Xu
First Name & Middle Initial & Last Name & Degree
Wei Guo
First Name & Middle Initial & Last Name & Degree
Jie Xu
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peng Zhang
First Name & Middle Initial & Last Name & Degree
Peng Zhang
Facility Name
Henan Provincial People's Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongxia Cui
First Name & Middle Initial & Last Name & Degree
Yongxia Cui
Facility Name
Union Hospital Tongji Medical College Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
100005
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Chen
First Name & Middle Initial & Last Name & Degree
Ting Ye
First Name & Middle Initial & Last Name & Degree
Jing Chen
First Name & Middle Initial & Last Name & Degree
Ting Ye
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410031
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xianan Li
First Name & Middle Initial & Last Name & Degree
Shuo Yang
First Name & Middle Initial & Last Name & Degree
Xianan Li
First Name & Middle Initial & Last Name & Degree
Shuo Yang
Facility Name
Shanghai Sixth People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200233
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Yao
First Name & Middle Initial & Last Name & Degree
Haiyan Hu
First Name & Middle Initial & Last Name & Degree
Yang Yao
First Name & Middle Initial & Last Name & Degree
Haiyan Hu
Facility Name
Tianjin Medical University Cancer Institude & Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jilong Yang
First Name & Middle Initial & Last Name & Degree
Jilong Yang
Facility Name
The Second Affiliated Hospital Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhaoming Ye
First Name & Middle Initial & Last Name & Degree
Binghao Li
First Name & Middle Initial & Last Name & Degree
Zhaoming Ye
First Name & Middle Initial & Last Name & Degree
Binghao Li

12. IPD Sharing Statement

Learn more about this trial

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

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