Osteosarcoma Metastatic

This phase II trial tests how well zanzalintinib (XL092) works in treating patients with leiomyosarcoma that has spread from where it first started to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Leiomyosarcomas are a type sarcoma that can occur in any location in the body, such as the uterus or in the abdomen. Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, interferes with cell communication and growth and may prevent tumor growth. Giving XL092 may kill more tumor cells in patients with metastatic or unresectable leiomyosarcoma. The trial has now been expanded to treat additional sarcoma types that are sensitive to tyrosine kinase inhibitors (TKIs) such as translocation-associated soft tissue sarcoma (such as synovial sarcoma), and bone sarcoma (including osteosarcoma and Ewing sarcoma).

This clinical study is the initiative of the FOSTER (Fight OsteoSarcoma Through European Research) consortium and Gustave Roussy, which is the sponsor. Its aim is to evaluate the biology of tumour in greater depth by collecting samples of the tumour during the biopsy at diagnosis, and blood samples. This study is a platform study that evolves over time. This means that it allows for the evaluation of several treatments or therapeutic strategies within a single clinical trial, which can be modified and adapted over time. The FOSTER evolving study platform aim to implement a comprehensive strategy of clinical, biological, radiological, therapeutic integrated research from diagnosis to relapse, with the aim to improve survival of osteosarcoma patients of all age, through randomised therapeutic questions at different phase of treatment from diagnosis to relapse. The platform study makes it possible to evaluate several treatments for the same disease, on an ongoing basis, using a main protocol with adaptable arms. The FOSTER-CabOS trial (part 2 of FOSTER study) is a European Phase III clinical study . It assesses the efficacy of cabozantinib, a tyrosine kinase inhibitor, as a maintenance therapy post-standard treatment in osteosarcoma patients. The trial is randomized against Best Supportive Care to determine the effectiveness of cabozantinib in improving event-free survival. This maintenance therapy aims to prevent relapse among patients who have already received standard treatment for osteosarcoma.

SOT106 is a special cancer medicine designed to find and kill certain cancer cells that carry a marker called LRRC15, while causing less harm to healthy cells. The study consists of two parts, Part A and Part B. The goal of Part A is to collect information about SOT106, understand its effects, and see whether it is safe and well tolerated at different dose levels. Part B of the study collects information on which of the two selected safe dose levels chosen in Part A gives the best balance between benefit and risk.

In advanced osteosarcoma where traditional chemotherapy has failed, the multi-targeted tyrosine kinase inhibitor apatinib has become a mainstream systemic treatment option in China. However, for patients with a high tumor burden or extra-pulmonary lesions, these drugs are prone to secondary resistance, necessitating combination with chemotherapy for more effective comprehensive control. Liposomal irinotecan, a newly approved topoisomerase inhibitor, exhibits lower toxicity compared to traditional irinotecan and is one of the second-line chemotherapy agents for osteosarcoma, making it a suitable candidate for combination therapy with apatinib. The primary objective of this study is to determine the optimal regimen of apatinib combined with liposomal irinotecan injection, while the secondary objective is to evaluate the safety and efficacy of this combination in patients with refractory osteosarcoma who have progressed after second-line chemotherapy.

Patients with pulmonary metastasis of osteosarcoma complicated with BPF often suffer from massive hemoptysis, refractory pneumothorax and difficult fistula healing due to tumor erosion of bronchial arteries. Traditional interventional embolization (such as simple coil or gelatin sponge embolization) has some limitations such as embolic material displacement, incomplete fistula closure and postoperative recurrent bleeding. Systemic chemotherapy and radiotherapy also have poor efficacy due to the complex blood supply of local lesions and poor tissue repair ability, and the quality of life of patients is seriously impaired. Therefore, there is an urgent need to explore a safer and durable precise embolization scheme. NBCA combined with coil closure is expected to break through the current technical bottleneck through the synergistic mechanism of "colloid embolization + mechanical occlusion". NBCA glue can quickly polymerize to achieve permanent occlusion of the micro vascular network, while the coil can strengthen the fistula through physical support. The combination of the two can not only accurately block abnormal blood supply, promote fistula healing, but also reduce the risk of embolus displacement and hemoptysis recurrence rate. This study is the first to systematically evaluate the efficacy and safety of this combination regimen in such patients, and provide key evidence for optimizing the embolization strategy and improving the long-term prognosis. The clinical transformation value and social significance of this study are significant. If NBCA combined with coil is proved to be effective in controlling bleeding, shortening fistula closure time and reducing complications, it will promote this technology to become the first choice for advanced osteosarcoma pulmonary metastasis with complex fistula. Its minimally invasive and repeatability can help to reduce the frequency of repeated hospitalization and the risk of infection, save medical resources, and provide new ideas for the exploration of multimodal embolization techniques in interventional medicine, which has a profound impact on improving the quality of life of patients with end-stage cancer.