Gefitinib + Trametinib + Disulfiram + Sunitinib for Osteosarcoma

This trial tests whether adding four drugs—gefitinib, trametinib, disulfiram (commonly used for alcohol dependence), and sunitinib—to standard chemotherapy can more effectively treat osteosarcoma, a type of bone cancer, compared to chemotherapy alone. Researchers aim to determine the safety of this new combination and understand how the cancer persists during treatment. Individuals with osteosarcoma that has spread and are either newly diagnosed or have relapsed may be suitable candidates, particularly if they have metastases that cannot be surgically removed or have had a complete response before relapsing. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents for osteosarcoma therapy or additional medicines specifically for treating cancer.

Previous studies have shown that disulfiram, used safely for over 60 years to treat alcohol abuse, is generally well-tolerated. Research indicates it can reduce tumor growth in osteosarcoma, similar to standard chemotherapy drugs, without causing additional severe side effects.

Gefitinib has been studied in over 2,400 lung cancer patients, and these studies suggest it is generally safe when used alone.

Sunitinib has been used in bone cancer patients and is considered to have manageable safety levels, although some patients stopped using it due to side effects like severe lung problems.

Trametinib, an FDA-approved drug for treating melanoma (a type of skin cancer), is used in lower doses for osteosarcoma. It is generally well-tolerated, though some patients may experience high blood pressure as a side effect.

Researchers are excited about these treatments for osteosarcoma because they offer new ways to target the cancer. Unlike traditional chemotherapy options like methotrexate, doxorubicin, and cisplatin, these drugs each bring something different to the table. Gefitinib and trametinib specifically target pathways involved in cancer cell growth, while sunitinib hits multiple targets, including tumor blood vessels. Disulfiram, usually used for alcohol dependency, is repurposed here to disrupt cancer cell survival mechanisms. Together, these treatments could potentially improve outcomes by tackling osteosarcoma from multiple angles.

Research has shown that disulfiram can significantly slow the spread of osteosarcoma, a type of bone cancer, in lab studies, working similarly to the chemotherapy drug doxorubicin. In this trial, participants may receive disulfiram as part of their treatment. Gefitinib, another treatment option in this trial, stops osteosarcoma from spreading by affecting certain immune cells called macrophages. Sunitinib, also under study in this trial, has shown promise in shrinking tumors and managing osteosarcoma effectively, especially when combined with other treatments, leading to longer periods without disease progression in some studies. Lastly, trametinib, which participants in this trial may receive, has effectively killed osteosarcoma cells by inducing cell death and blocking specific growth signals. These findings suggest that these drugs could be part of a treatment plan for osteosarcoma.¹²⁴⁵⁶