A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

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: Not yet recruiting
• Conditions: Osteosarcoma
• Intervention / Treatment: Drug: Etoposide; Drug: Isophosphamide; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 148
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhaoming Ye, PhD; Phone Number: 13606501549; Email: yezhaoming@zju.edu.cn
• Study Contact Backup: Name: zengjie zhang, MD; Phone Number: 19858877686; Email: zengjiezhang@zju.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University People's Hospital
      • Contact: Yi Yang, PhD; Phone Number: 13701312827; Email: 13701312827@163.com
  • 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: Weibin Zhang, PhD; Phone Number: 13501824630; Email: zhangweibin10368@163.com
    • 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: Sung Taek Jung, PhD; Email: stjung@jnu.ac.kr

Participation Criteria

Eligibility Criteria

• 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.

-

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best of response,BOR	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)	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

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: 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: 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

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: October 19, 2022
• First Submitted That Met QC Criteria: October 19, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Etoposide; Ifosfamide; Tyrosine kinase inhibitors; Refractory or Relapsed osteosarcoma; Sulfatinib
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Ifosfamide
• Other Study ID 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