Intra-arterial Cisplatin Plus Rh-endostatin Combined With Systematic Chemotherapy in Osteosarcoma

Trial Title: Intra-arterial Cisplatin Plus Rh-endostatin Combined With Systematic Chemotherapy in Osteosarcoma

NCT ID: NCT06562673

Condition: Osteosarcoma
Bone Cancer

Conditions: Official terms:
Osteosarcoma
Bone Neoplasms
Endostar protein
Endostatins
Angiogenesis Inhibitors

Conditions: Keywords:
osteosarcoma
intra-arterial
anti-angiogenesis inhibitor
endostatin
cisplatin

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: intra-arterial cisplatin plus anti-angiogenesis inhibitor rh-endostatin (Endostar)
Description: After insertion of a catheter percutaneously by using the Seldinger technique through the brachial or femoral artery under local anesthesia, rh-endostatin was administered intra-arterially with dosage of 150 mg for a 6-h continuous infusion; then cisplatin was administered intra-arterially at 120 mg/m2 as a 6-h continuous infusion.
Arm group label: IA cisplatin plus endostatin

Other name: intra-arterial treatment

Summary: The goal of this clinical trial is to learn the efficacy and safety of intra-arterial cisplatin plus anti-angiogenesis inhibitor rh-endostatin (Endostar) combined with systematic chemotherapy in osteosarcoma. The main questions it aims to answer are: - Is it safe when rh-endostatin and cisplatin are administered intra-arterially? - Does intra-arterial cisplatin plus rh-endostatin increase the rate of tumor necrosis compared with traditional treatment? Researchers will treat newly diagnosed osteosarcoma patients with systematic treatment and local treatment. For systematic treatment, regular high-dose methotrexate and adriamycin will be administered intravenously. For local treatment, rh-endostatin was administered intra-arterially with dosage of 150 mg for a 6-h continuous infusion; then cisplatin was administered intra-arterially at 120 mg/m2 as a 6-h continuous infusion. Local treatment is conducted by insertion of a catheter percutaneously using the Seldinger technique through the brachial or femoral artery under local anesthesia. Participants will: • Receive local combined with systematic treatment once every 2-3 weeks for 2-4 cycles before surgery.

Detailed description: Osteosarcoma (OS) is the most common bone cancer in children and young adolescents. Despite the emergence of new therapeutic modalities such as targeted therapy and immunotherapy, chemotherapy remains the standard treatment. The current standard treatment for osteosarcoma is the preoperative chemotherapy, surgery and postoperative chemotherapy. Preoperative chemotherapy (or neoadjuvant chemotherapy) and neoadjuvant chemotherapeutic agents include cisplatin, adriamycin, methotrexate. The use of preoperative chemotherapy has increased the 5-year survival rate from 20% to 60%-70%. Over the past 40 years, limited progress has been made in improving survival outcomes in patients with OS. Transcatheter arterial infusion (TAI) is the direct infusion of drugs in the tumor blood supply artery, which can overcome the physiological barrier that some intravenous drug can not pass, thus significantly increasing the local drug concentration in the tumor and improving the therapeutic efficacy. Studies have shown that the combination of intravenous doxorubicin and intra-arterial cisplatin infusion before surgery resulted in a favorable histological response in 87% of enrolled patients, with a 10-year survival rate of 93% and an event-free survival rate of 86%. Recombinant endostatin, an anti-angiogenic drug approved by the National Medical Products Administration of China in 2005 for the treatment of non-small cell lung cancer. In preclinical studies, synergistic antitumor efficacy was observed in an osteosarcoma mouse model with the addition of rh-endostatin to doxorubicin. In the clinical study of osteosarcoma, after comparing 58 patients with stage IIB osteosarcoma treated with chemotherapy combined with endostatin and 272 patients treated with chemotherapy alone, results show that the 5-year DMFS (distant metastasis-free survival) of the control group (61%) was significantly lower than that of the rh-endostatin group (79%) (P = 0.013). The 5-year OS of the control group (74%) was significantly lower than that of the rh-endostatin treatment group (87%) (P = 0.029). These results suggest that endostatin combined with chemotherapy for osteosarcoma significantly improves distant metastasis-free survival, with tolerable adverse effects, and is worthy of further clinical investigation. Therefore, the investigators propose that arterial infusion of endostatin and cisplatin combined with systematic therapy might improve the treatment efficacy in preoperative course.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of osteosarcoma patients aged 18-40 years old; 2. Accept to receive treatment with neoadjuvant chemotherapy regimen and completing the standard treatment course; Voluntary informed consent, joining the study with good compliance. 3. Have detailed medical data (such as medical history data, laboratory reports of blood routine and liver and kidney functions, pathology reports, etc.), and complete records of postoperative follow-up. Exclusion Criteria: 1. Combined history of acute injury, infection and surgery in the last 3 months; 2. Those with severe liver and kidney function abnormalities; 3. Those who are using anti-inflammatory drugs; 4. Pre-existing hematologic diseases before treatment; 5. Combined with other malignant tumors; 6. Diagnosed with autoimmune disease or using steroid drugs for more than 1 month before treatment; 7. Suffering from mental illness or cognitive dysfunction.

Gender: All

Minimum age: 18 Years

Maximum age: 40 Years

Healthy volunteers: No

Locations:

Facility:
Name: Shanghai Jiao Tong University School of Medicine, Shanghai Sixth People's Hospital,

Address:
City: Shanghai
Zip: 200233
Country: China

Contact:
Last name: Hong-Tao Li, Dr.

Phone: +86-021-24058430
Email: Lhtmed@shsmu.edu.cn

Contact backup:
Last name: Yong-Gang Wang, Dr.

Phone: +86-021-24058430
Email: sirui666@163.com

Investigator:
Last name: Hong-Tao Li, Dr.
Email: Principal Investigator

Investigator:
Last name: Yong-Gang Wang, Dr.
Email: Principal Investigator

Start date: August 20, 2024

Completion date: April 20, 2025

Lead sponsor:
Agency: Shanghai 6th People's Hospital
Agency class: Other

Source: Shanghai 6th People's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06562673