search
Back to results

A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

Primary Purpose

Osteosarcoma

Status
Not yet recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Sulfatinib
Etoposide
Isophosphamide
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteosarcoma focused on measuring Refractory or Relapsed osteosarcoma, Sulfatinib, Tyrosine kinase inhibitors, Etoposide, Ifosfamide

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Osteosarcoma subjects Male or female participants aged 2 to 25 years at the time of informed consent(Histologically or cytologically confirmed diagnosis of high grade osteosarcoma)
  2. Recurrent or refractory solid tumor malignancies that have treated with standard anticancer therapy but have no available treatment options.
  3. Evaluable or measurable disease that met the following criteria: 1. Participants must have an evaluable or measurable disease based on RECIST 1.1, using computed tomography (CT)/ magnetic resonance imaging (MRI). 2. Lesions that have been treated locally, such as external beam radiation therapy (EBRT) or radiofrequency (RF) ablation, must subsequently grow clearly to be considered target lesions.
  4. Life expectancy is 3 months or more.
  5. Adequate bone marrow function : ①. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L. ②. Hemoglobin ≥ 8.0 g/ deciliter (hemoglobin ≤ 8.0 g/ deciliter is acceptable if corrected by growth factors or transfusion before starting sovanitinib). ③. Platelet count ≥ 75 x 10^9/L.
  6. Adequate liver function: 1. Bilirubin ≤ 1.5 times the upper limit of normal (ULN). 2. Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times of ULN.
  7. Adequate renal function, such as creatinine clearance (or radioisotope glomerular filtration rate [GFR]), must be greater than 70 mL/min/ 1.73 square meters.

(8)A baseline left ventricular ejection fraction (LVEF) of 50% or greater, as determined by echocardiography, indicates adequate cardiac function.

(9) Good control of blood pressure (BP) with or without antihypertensive medication was defined as : blood pressure below 95% for sex, age, and height/length at screening (according to National Heart, Lung, and Blood Institute guidelines) and no change in antihypertensive medication during the cycle 1 of project. participants with osteosarcoma had blood pressure ≤150/90 mm Hg at screening and had no change in antihypertensive therapy during the cycle 1 of project.

(10)Parents or legal representative (guardian) shall sign the written informed consent and obtain the consent of minor participants. Written informed consent from subjects ≥18 years of age. Willing and able to abide by the researchers determine solutions, plans, and toxicity of follow-up management.

Exclusion Criteria:

  1. Any active infection or infectious disease.
  2. Any medical condition or other condition that the investigator believes will prevent the participant from participating in the clinical study.
  3. Other organ toxicity (except hair loss) caused by previous anti-cancer treatment (research drug, chemotherapy or radiotherapy)
  4. Known hypersensitivity to any component of the product (soventinib or ingredient).
  5. Any other anti-tumor treatment is given at the same time.
  6. He has been treated with sovantinib before.
  7. Two or more previous VEGF/VEGFR targeted therapies.
  8. Currently receiving any study drug or device in another clinical trial or within 30 days before informed consent.
  9. Clinically significant ECG abnormalities, including significant baseline QT or QTc interval prolongation (e.g., QTc interval duplication is demonstrated to be greater than 480 milliseconds).
  10. Gastrointestinal malabsorption or any other condition that the investigator believes may affect the absorption of sovantinib.
  11. Gastrointestinal bleeding or active hemoptysis (at least half a teaspoon of bright red blood) occurred within 3 weeks before the first administration of the study drug.
  12. Active second malignant tumor (excluding superficial melanoma, in situ, basal or squamous cell skin cancer with definite treatment) within 2 years before enrollment.
  13. Previously treated with ifosfamide with nephrotoxicity or encephalopathy grade greater than or equal to grade 3.

Women who were breastfeeding or pregnant at the time of screening or baseline. If a negative screening pregnancy test is obtained more than 72 hours before the first administration of the study drug, a separate baseline assessment is required.

-

Sites / Locations

  • Peking University People's Hospital
  • Qilu Hospital of Shandong University
  • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
  • Department of Orthopaedic Surgery, Sixth People's Hospital, Shanghai Jiao Tong University,
  • Department of Orthopedic Surgery Chonnam National University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Etoposide plus Ifosfamide group

Etoposide plus Ifosfamide Combined With Sulfatinib

Arm Description

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Outcomes

Primary Outcome Measures

4 months progression-free survival
The proportion of patients who had no objective tumor progression or death from the start of treatment to 4 months of follow-up.
Efficacy evaluation in solid tumors
Complete response (CR), all target and non-target lesions (non-lymph nodes) disappear, and the diameter of all pathologic lymph nodes (both target and non-target) must be reduced to <10 mm; Partial response (PR), using baseline total diameter as reference, reduced the total diameter of target lesions by at least 30%.

Secondary Outcome Measures

Best of response,BOR
From the date of the first administration of the study drug to disease progression or death, whichever occurs first.
Duration of Remission (DOR)
Complete response (CR)/ partial response (PR) was first recorded until disease progression was first recorded until the data cutoff date.

Full Information

First Posted
October 19, 2022
Last Updated
October 19, 2022
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Chonnam National University, Peking University People's Hospital, Qilu Hospital of Shandong University, Ruijin Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05590572
Brief Title
A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma
Official Title
A Study of Etoposide and Ifosfamide Combined With or Without Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Chonnam National University, Peking University People's Hospital, Qilu Hospital of Shandong University, Ruijin Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

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 is a phase 1/2 study evaluating safety, tolerability, and efficacy of Sulfatinib in combination with chemotherapy (ifosfamide and etoposide) in children and adolescents with refractory or relapsed osteosarcoma ( combination Sulfatinib).
Detailed Description
The study consists of 2 cohorts: Cohort 1 (Traditional chemotherapy) will evaluate the efficacy of ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma. Cohort 2 (Combination Expansion) will evaluate the efficacy of Sulfatinib in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma. Sulfatinib will be provided as hard capsules containing 300 mg Sulfatinib. Sulfatinib capsules should be dissolved in water or apple juice for those who are unable to swallow capsules.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma
Keywords
Refractory or Relapsed osteosarcoma, Sulfatinib, Tyrosine kinase inhibitors, Etoposide, Ifosfamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
148 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Etoposide plus Ifosfamide group
Arm Type
Active Comparator
Arm Description
Children and adolescents with relapsed or refractory drug resistant osteosarcoma
Arm Title
Etoposide plus Ifosfamide Combined With Sulfatinib
Arm Type
Experimental
Arm Description
Children and adolescents with relapsed or refractory drug resistant osteosarcoma
Intervention Type
Drug
Intervention Name(s)
Sulfatinib
Intervention Description
(1) Sulfatinib: 300 mg, oral once a day (QD), 21 days as a cycle
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
(1) Etoposide: 100 mg/m2/day (initial dose) will be administered on the first to third days of each 21 day cycle, a total of 5 cycles. The dose of etoposide can be reduced to 80 mg/m2/day and 60 mg/m2/day.;
Intervention Type
Drug
Intervention Name(s)
Isophosphamide
Intervention Description
(1) Isophosphamide: 3000 mg/m2/day (initial dose) will be administered on the first to third days of each 21 day cycle for 5 cycles. The dose of ifosfamide can be reduced to 2400 mg/m2/day and 1800 mg/m2/day.
Primary Outcome Measure Information:
Title
4 months progression-free survival
Description
The proportion of patients who had no objective tumor progression or death from the start of treatment to 4 months of follow-up.
Time Frame
4 months
Title
Efficacy evaluation in solid tumors
Description
Complete response (CR), all target and non-target lesions (non-lymph nodes) disappear, and the diameter of all pathologic lymph nodes (both target and non-target) must be reduced to <10 mm; Partial response (PR), using baseline total diameter as reference, reduced the total diameter of target lesions by at least 30%.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Best of response,BOR
Description
From the date of the first administration of the study drug to disease progression or death, whichever occurs first.
Time Frame
4 months
Title
Duration of Remission (DOR)
Description
Complete response (CR)/ partial response (PR) was first recorded until disease progression was first recorded until the data cutoff date.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Osteosarcoma subjects Male or female participants aged 2 to 25 years at the time of informed consent(Histologically or cytologically confirmed diagnosis of high grade osteosarcoma) Recurrent or refractory solid tumor malignancies that have treated with standard anticancer therapy but have no available treatment options. Evaluable or measurable disease that met the following criteria: 1. Participants must have an evaluable or measurable disease based on RECIST 1.1, using computed tomography (CT)/ magnetic resonance imaging (MRI). 2. Lesions that have been treated locally, such as external beam radiation therapy (EBRT) or radiofrequency (RF) ablation, must subsequently grow clearly to be considered target lesions. Life expectancy is 3 months or more. Adequate bone marrow function : ①. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L. ②. Hemoglobin ≥ 8.0 g/ deciliter (hemoglobin ≤ 8.0 g/ deciliter is acceptable if corrected by growth factors or transfusion before starting sovanitinib). ③. Platelet count ≥ 75 x 10^9/L. Adequate liver function: 1. Bilirubin ≤ 1.5 times the upper limit of normal (ULN). 2. Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times of ULN. Adequate renal function, such as creatinine clearance (or radioisotope glomerular filtration rate [GFR]), must be greater than 70 mL/min/ 1.73 square meters. (8)A baseline left ventricular ejection fraction (LVEF) of 50% or greater, as determined by echocardiography, indicates adequate cardiac function. (9) Good control of blood pressure (BP) with or without antihypertensive medication was defined as : blood pressure below 95% for sex, age, and height/length at screening (according to National Heart, Lung, and Blood Institute guidelines) and no change in antihypertensive medication during the cycle 1 of project. participants with osteosarcoma had blood pressure ≤150/90 mm Hg at screening and had no change in antihypertensive therapy during the cycle 1 of project. (10)Parents or legal representative (guardian) shall sign the written informed consent and obtain the consent of minor participants. Written informed consent from subjects ≥18 years of age. Willing and able to abide by the researchers determine solutions, plans, and toxicity of follow-up management. Exclusion Criteria: Any active infection or infectious disease. Any medical condition or other condition that the investigator believes will prevent the participant from participating in the clinical study. Other organ toxicity (except hair loss) caused by previous anti-cancer treatment (research drug, chemotherapy or radiotherapy) Known hypersensitivity to any component of the product (soventinib or ingredient). Any other anti-tumor treatment is given at the same time. He has been treated with sovantinib before. Two or more previous VEGF/VEGFR targeted therapies. Currently receiving any study drug or device in another clinical trial or within 30 days before informed consent. Clinically significant ECG abnormalities, including significant baseline QT or QTc interval prolongation (e.g., QTc interval duplication is demonstrated to be greater than 480 milliseconds). Gastrointestinal malabsorption or any other condition that the investigator believes may affect the absorption of sovantinib. Gastrointestinal bleeding or active hemoptysis (at least half a teaspoon of bright red blood) occurred within 3 weeks before the first administration of the study drug. Active second malignant tumor (excluding superficial melanoma, in situ, basal or squamous cell skin cancer with definite treatment) within 2 years before enrollment. Previously treated with ifosfamide with nephrotoxicity or encephalopathy grade greater than or equal to grade 3. Women who were breastfeeding or pregnant at the time of screening or baseline. If a negative screening pregnancy test is obtained more than 72 hours before the first administration of the study drug, a separate baseline assessment is required. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhaoming Ye, PhD
Phone
13606501549
Email
yezhaoming@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
zengjie zhang, MD
Phone
19858877686
Email
zengjiezhang@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
zhaoming Ye, PhD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Binhao Li, PhD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
zengjie zhang, MD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shengdong Wang, MD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xin Huang, PhD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peng Lin, MD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Yang, PhD
Phone
13701312827
Email
13701312827@163.com
Facility Name
Qilu Hospital of Shandong University
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Li, PhD
Phone
13668812855
Facility Name
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weibin Zhang, PhD
Phone
13501824630
Email
zhangweibin10368@163.com
Facility Name
Department of Orthopaedic Surgery, Sixth People's Hospital, Shanghai Jiao Tong University,
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200233
Country
China
Facility Name
Department of Orthopedic Surgery Chonnam National University
City
Donggu
State/Province
Gwangju
ZIP/Postal Code
999007
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung Taek Jung, PhD
Email
stjung@jnu.ac.kr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

We'll reach out to this number within 24 hrs