A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

October 19, 2022 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

A Study of Etoposide and Ifosfamide Combined With or Without Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
148

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100000
        • Peking University People's Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250000
        • Qilu Hospital of Shandong University
        • Contact:
          • Zhenfeng Li, PhD
          • Phone Number: 13668812855
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:
      • Shanghai, Shanghai, China, 200233
        • Department of Orthopaedic Surgery, Sixth People's Hospital, Shanghai Jiao Tong University,
  • Korea, Republic of
    • Gwangju
      • Donggu, Gwangju, Korea, Republic of, 999007
        • Department of Orthopedic Surgery Chonnam National University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Etoposide plus Ifosfamide group
Children and adolescents with relapsed or refractory drug resistant osteosarcoma
Drug: Etoposide
(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.;
Drug: Isophosphamide
(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.
Experimental: Etoposide plus Ifosfamide Combined With Sulfatinib
Children and adolescents with relapsed or refractory drug resistant osteosarcoma
Drug: Etoposide
(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.;
Drug: Isophosphamide
(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.
Drug: Sulfatinib
(1) Sulfatinib: 300 mg, oral once a day (QD), 21 days as a cycle

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
4 months progression-free survival
Time Frame: 4 months
The proportion of patients who had no objective tumor progression or death from the start of treatment to 4 months of follow-up.
4 months
Efficacy evaluation in solid tumors
Time Frame: 2 months
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%.
2 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Best of response,BOR
Time Frame: 4 months
From the date of the first administration of the study drug to disease progression or death, whichever occurs first.
4 months
Duration of Remission (DOR)
Time Frame: 2 years
Complete response (CR)/ partial response (PR) was first recorded until disease progression was first recorded until the data cutoff date.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Peking University People's Hospital
Qilu Hospital of Shandong University
Ruijin Hospital
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Chonnam National University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: zhaoming Ye, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Study Director: Binhao Li, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: zengjie zhang, MD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: Shengdong Wang, MD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: Xin Huang, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: Peng Lin, MD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2023

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 21, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 21, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022-0880

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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