The goal of this clinical trial is to see if adding a weight loss medication (GLP-1 receptor drug) to patients with an increased BMI receiving treatment for rectal cancer prior to surgery (total neoadjuvant chemoradiotherapy) improves cancer outcomes. The main questions it aims to answer is 1. Does the drug increase weight loss in rectal cancer patients with a high BMI 2. Does the drug improve response rates to chemotherapy and radiotherapy 3. Does the drug improve survival outcomes and if cancer returns Researchers will compare this drug in one group against a group of patients receiving preoperative total neoadjuvant chemoradiotherapy without the drug Patients will be required to 1\) take the GLP-1 receptor agonist drug during TNT or just having TNT alone as per standard hospital protocols Body weight will be measured at three predefined time points: 1. Baseline: Prior to initiation of semaglutide or TNT 2. Pre-TNT: Start of TNT (for the intervention arm, this is 4 weeks after semaglutide initiation) 3. Post-TNT: Within 7 days following completion of TNT and prior to definitive surgery Patients will complete their treatment and go on to have surgery as per standard methods for treating rectal cancer
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Weight Loss
Timeframe: 6 months
Metabolic Profile of the Tissue
Timeframe: From enrolment to operation within 1 year
Inflammatory Mediators
Timeframe: From enrolment to surgical resection within 1 year
GLP-1 effects on mitochondrial fitness
Timeframe: From enrolment to surgical resection within 1 year
Mapping systemic inflammatory profiles
Timeframe: From enrolment to surgical resection within 1 year
Mapping circulating immune systems
Timeframe: From enrolment to surgical resection within 1 year
Mapping tumour resident immune system
Timeframe: From enrolment to surgical resection within 1 year