A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

NCT05590572 | Not Yet Recruiting Phase 1

• 1 other identifier: 2022-0880
• Study Type: interventional
• Target: 148
• Locations: 2 countries
• Sites: 5

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).

Conditions

Osteosarcoma

Keywords

Refractory or Relapsed osteosarcoma; Sulfatinib; Tyrosine kinase inhibitors; Etoposide; Ifosfamide

Outcome Measures

Primary Outcomes (2)

• 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.

  4 months

• 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%.

  2 months

Secondary Outcomes (2)

• Best of response,BOR

  4 months

• Duration of Remission (DOR)

  2 years

Study Arms (2)

Etoposide plus Ifosfamide group

ACTIVE COMPARATOR

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Drug: Etoposide; Drug: Isophosphamide

Etoposide plus Ifosfamide Combined With Sulfatinib

EXPERIMENTAL

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Drug: Sulfatinib; Drug: Etoposide; Drug: Isophosphamide

Interventions

Sulfatinib DRUG

(1) Sulfatinib: 300 mg, oral once a day (QD), 21 days as a cycle

Etoposide plus Ifosfamide Combined With Sulfatinib

Etoposide DRUG

(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.;

Etoposide plus Ifosfamide Combined With Sulfatinib; Etoposide plus Ifosfamide group

Isophosphamide DRUG

(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.

Etoposide plus Ifosfamide Combined With Sulfatinib; Etoposide plus Ifosfamide group

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Chonnam National University: collaborator
• Peking University People's Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Ruijin Hospital: collaborator
• Shanghai Jiao Tong University Affiliated Sixth People's Hospital: collaborator

Study Sites (5)

Peking University People's Hospital

Beijing, Beijing Municipality, 100000, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, 250000, China

Location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200000, China

Location

Department of Orthopaedic Surgery, Sixth People's Hospital, Shanghai Jiao Tong University,

Shanghai, Shanghai Municipality, 200233, China

Location

Department of Orthopedic Surgery Chonnam National University

Donggu, Gwangju, 999007, South Korea

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

surufatinib; Etoposide; Ifosfamide

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• zhaoming Ye, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY CHAIR

• Binhao Li, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhaoming Ye, PhD

CONTACT

13606501549; yezhaoming@zju.edu.cn

zengjie zhang, MD

CONTACT

19858877686; zengjiezhang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: October 21, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 21, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4); KR (1)