A Study of Sulfatinib on Relapsed or Refractory Drug Resistant Osteosarcoma

NCT ID: NCT05590572

Last Updated: 2022-10-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2027-12-31

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.

Conditions

Osteosarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Etoposide plus Ifosfamide group

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Group Type: ACTIVE_COMPARATOR

Etoposide

Intervention Type: 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.;

Isophosphamide

Intervention Type: 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

Children and adolescents with relapsed or refractory drug resistant osteosarcoma

Group Type: EXPERIMENTAL

Sulfatinib

Intervention Type: DRUG

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

Etoposide

Intervention Type: 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.;

Isophosphamide

Intervention Type: 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.

Interventions

Sulfatinib

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

Intervention Type: 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.;

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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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• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chonnam National University

OTHER

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

zhaoming Ye, PhD

Role: STUDY_CHAIR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Binhao Li, PhD

Role: STUDY_DIRECTOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

zengjie zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Shengdong Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Xin Huang, PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Peng Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Locations

Peking University People's Hospital

Beijing, Beijing Municipality, China

Qilu Hospital of Shandong University

Jinan, Shandong, China

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

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

Shanghai, Shanghai Municipality, China

Department of Orthopedic Surgery Chonnam National University

Donggu, Gwangju, South Korea

Countries

China; South Korea

Central Contacts

Zhaoming Ye, PhD

Role: CONTACT

yezhaoming@zju.edu.cn

13606501549

zengjie zhang, MD

Role: CONTACT

zengjiezhang@zju.edu.cn

19858877686

Facility Contacts

Yi Yang, PhD

Role: primary

13701312827@163.com

13701312827

Zhenfeng Li, PhD

Role: primary

13668812855

Weibin Zhang, PhD

Role: primary

zhangweibin10368@163.com

13501824630

Sung Taek Jung, PhD

Role: primary

stjung@jnu.ac.kr

Other Identifiers

2022-0880

Identifier Type: -

Identifier Source: org_study_id