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
Written informed consent according to local guidelines obtained prior to any study-related activities.
Histologically confirmed mismatch repair protein proficient adenocarcinoma of the rectum.
BMI ≥25 kg/m²
Radiological confirmed >T2, Node positive, Threatened Surgical Margin and/or EMVI+ by MRI
Received prior chemotherapy or radiotherapy
Previous or concurrent active malignancy ≤ 5 years prior to registration, with the exception of non-melanotic skin cancer or carcinoma in situ of any type, or other cancers that the treating investigator does not feel will impact the study objectives.
Locally advanced disease T3N+ or T4 disease.
Recurrent rectal cancer