Locally Advanced Clear Cell Renal Cell Carcinoma

The purpose of this study is to compare the safety and effectiveness of two new treatments: belzutifan alone or belzutifan in combination with pembrolizumab before kidney surgery and followed by a combination of belzutifan and pembrolizumab treatment post-surgery. Belzutifan is a small molecule drug that specifically blocks a protein called Hypoxia-Inducible Factor 2 alpha (HIF-2α) and slows down or stops the growth of cancer. Belzutifan has been shown to provide better treatment results in kidney cancer compared to other drugs that target similar proteins to stop cancer growth. Pembrolizumab is a type of medicine called an immunotherapy drug. It helps the immune system spot and attack kidney cancer cells by blocking a "stop sign" that the cancer uses to hide and help slow down or shrink the cancer. The combined use of molecules similar to belzutifan and pembrolizumab has shown promising results in treating kidney cancer, although effectiveness depends on the specific combination. This treatment combination is experimental and is not approved to treat kidney cancer in Australia. This means that it must be tested to see if it is an effective treatment combination for kidney cancer prior to kidney surgery.

This phase I/II trial tests the safety and effectiveness of inulin gel in combination with ipilimumab and nivolumab in treating patients with kidney cell cancer (renal cell carcinoma \[RCC\]) that has spread from where it first started (primary site) to other places in the body (metastatic) or has spread to nearby tissue or lymph nodes (locally advanced). Inulin is a common food additive fermentable prebiotic fiber beneficial for a healthy gut microbiome. The microbiome is the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on and inside the body. Inulin may also be used for cancer prevention and heart health, but there is less evidence to support those uses. The gut microbiome profile may improve the effectiveness of drugs called immune checkpoint inhibitors, such as ipilimumab and nivolumab. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving inulin gel in combination with ipilimumab and nivolumab may be safe and effective in treating in patients with metastatic or locally advanced RCC.

This phase I trial tests the safety and effectiveness of 18F-TRX in detecting tumors (cancer) patients with solid tumors. 18F-TRX is an imaging tracer that is used to visualize tumors using a PET scan. It specifically targets and detects labile (unstable) iron levels within tissues, including tumors. Diagnostic procedures, such as 18F-TRX PET/CT or PET/MRI, may help detect tumors in patients with solid tumors