Trial Title:
A Clinical Study of Surufatinib Combined With Chemotherapy as Neoadjuvant Treatment in Osteosarcoma
NCT ID:
NCT05926492
Condition:
Osteosarcoma
Conditions: Official terms:
Osteosarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Surufatinib plus chemotherapy
Description:
Surufatinib: (1) for patients aged > 21 years old and ≤70 years old, surufatinib 200 mg,
qd, oral, continuous administration; (2) For patients aged ≥2 years and ≤21 years,
starting from the low dose of patient BSA (body surface area), Stevenson's formula
developed according to the Chinese population was used: BSA = 0.0061H+0.0128W-0.1529 (H:
BSA = 0.0061H+0.0128W-0.1529). Height /cm; W: body weight /kg); Chemotherapy : 1)
Doxorubicin 60 mg/m2, or liposome doxorubicin 45mg/ m2, day 17; 2) Cisplatin: 100 mg/m2,
day 15; 3) Ifosfamide; 2.5g/m2, day 8-12;
The above drugs were used in turn, and 30 days were regarded as a treatment cycle.
Arm group label:
Surufatinib plus chemotherapy
Other name:
Arm A
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
1) High-dose methotrexate : 8-12 g/m2 (MTX chemotherapy requires blood drug
concentration monitoring), day 1 and 8; 2) Doxorubicin 60 mg/m2 or liposomal
doxorubicin 45mg/ m2, day 17; 3) Cisplatin: 100 mg/m2, day 15;4) Ifosfamide; 2.5
g/m2, day 8-12.
The above drugs were used in turn, and 30 days were regarded as a treatment cycle.
Arm group label:
Chemotherapy
Other name:
Arm B
Summary:
This phase II study aims to explore the tumor necrosis rate in osteosarcoma patients
treated with a neoadjuvant regimen of surufatinib combined with chemotherapy.
Detailed description:
Surufatinib is a potent inhibitor of colony-stimulating factor 1 receptor（CSF-1R）, which
shows a promising tumor inhibition effect on sarcoma. This is a prospective, multicenter,
controlled phase II study to explore the efficacy and safety of surufatinib combined with
chemotherapy in neoadjuvant treatment of osteosarcoma. In this study, 160 patients were
enrolled into the following treatment groups with a 1:1 ratio: (1) Surufatinib +
chemotherapy group (N=80) (2) control group: chemotherapy group (N=80); A 30-day
treatment cycle was performed, the efficacy was evaluated after 2 cycles of neoadjuvant
therapy. The primary endpoints were tumor necrosis rate, and secondary endpoints were
1-year progression-free survival (PFS) and drug safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Have fully understood the study and voluntarily signed the informed consent;
2. Age from 2 to 70 years old (inclusive), both male and female;
3. histologically or cytologically confirmed diagnosis of primary bone tumor
4. having at least one measurable lesion (RECIST 1.1);
5. The patient has not been treated before (including any chemotherapy, targeting,
immune and other drugs);
6. The functions of major organs and bone marrow are basically normal;
7. ECOG performance status 0 or 1 (PS 0-2 points for amputees);
8. Expected survival ≥12 weeks;
9. Blood test (without blood transfusion within 14 days) 1) Neutrophil absolute value
≥1.5×109/L, platelets ≥100×109/L, hemoglobin concentration ≥9g/dL); 2) Liver
function test (aspartate aminotransferase and glutamic aminotransferase ≤2.5×ULN,
total bilirubin ≤1.5×ULN; In case of liver metastasis, AST and ALT≤5×ULN); 3) Renal
function (serum creatinine ≤1.5×ULN, creatinine clearance (CCr)≥60ml/min);
10. Fertile male or female patients voluntarily used effective contraceptive methods,
such as double barrier methods, condoms, oral or injectable contraceptives,
intrauterine devices, etc., during the study period and within 6 months of the last
study dose. All female patients will be considered fertile unless the female patient
has undergone natural menopause, artificial menopause or sterilization (such as
hysterectomy, bilateral adnexectomy or radiation of the ovary).
Exclusion Criteria:
1. Patients who have previously received chemotherapy drugs, surufatinib, or other
antiangiogenic agents;
2. Received approved or under development systematic anti-tumor therapy within 4 weeks
before enrollment, including chemotherapy, radical radiotherapy, biological
immunotherapy, targeted therapy, etc.;
3. Received any surgery or invasive treatment or operation (except intravenous
catheterization, puncture drainage, etc.) within 4 weeks before enrollment;
4. International Standardized Ratio (INR)> 1.5 or partially activated prothrombin time
(APTT) > 1.5×ULN;
5. The investigator identified clinically significant electrolyte abnormalities;
6. The patient currently has hypertension that cannot be controlled by drugs, as
follows: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
7. Unsatisfactory blood glucose control (FBG > 10 mmol/L);
8. The patient has any current disease or condition that affects the absorption of the
drug, or the patient cannot take surufatinib orally;
9. The patient currently has gastrointestinal diseases such as active gastric and
duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or
other conditions determined by researchers that may cause gastrointestinal bleeding
or perforation;
10. Patients with evidence or history of significant bleeding tendency within 3 months
prior to enrollment (bleeding >30 mL within 3 months , hematemesis, stool, stool
blood), hemoptysis ( > 5 mL of fresh blood within 4 weeks) or had a thromboembolic
event (including stroke events and/or transient ischemic attacks) within 12 months;
11. Clinically significant cardiovascular disease, including but not limited to the
following: acute myocardial infarction, severe/unstable angina pectoris, or coronary
artery bypass grafting within 6 months prior to enrollment; New York Heart
Association (NYHA) Grades for Congestive Heart Failure was > level 2; Ventricular
arrhythmias requiring medical treatment; LVEF (Left ventricular Ejection Fraction) <
50%;
12. Have had other malignancies within the past 5 years, except basal cell or squamous
cell carcinoma of the skin after radical surgery, or carcinoma in situ of the
cervix;
13. Active or uncontrolled severe infection; 1) Known human immunodeficiency virus (HIV)
infection; 2) Known history of clinically significant liver disease, including viral
hepatitis [active HBV infection, i.e., HBV DNA positive (> 1×104 copies /mL or >
2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers; 3) Known
hepatitis C virus infection (HCV) and HCV RNA positive (> 1×103 copies /mL), or
other hepatitis, cirrhosis;
14. The patient has current central nervous system (CNS) metastases or previous brain
metastases;
15. Patients with persistent toxicity due to any previous antitumor therapy that has not
returned to ≤ grade 2, but with alopecia or lymphocytopenia of any grade are
admitted to this study;
16. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
17. Received blood transfusion therapy, blood products and hematopoietic factors, such
as albumin and granulocyte colony-stimulating factor (G-CSF), within 14 days before
enrollment;
18. Any other medical condition, clinically significant metabolic abnormality, physical
abnormality or laboratory abnormality, which, in the investigator's judgment,
reasonably suspects that the patient has a medical condition or condition that is
not suitable for the use of the investigational drug (such as having seizures and
requiring treatment), or which would affect the interpretation of the study results
or place the patient at high risk;
19. Urine routine indicated urinary protein ≥2+, and 24-hour urinary protein
quantification >1.0g.
Gender:
All
Minimum age:
2 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhaoming Ye, M.D.
Phone:
0086 13606501549
Email:
yezhaoming@zju.edu.cn
Start date:
January 9, 2024
Completion date:
July 2026
Lead sponsor:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Source:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05926492
