Clinical trial
Evaluating the Impact of GLP-1 Receptor Agonists With Total Neoadjuvant Therapy in Rectal Cancer
Opening soon · Phase 2 · 0 countries · Registry ID NCT07314528
What this study is about
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
Basic eligibility
Full registry criteria
Treatments and study arms
GLP-1 receptor agonist
All patients will receive standard total neoadjuvant therapy for rectal cancer as per local standards. One group will receive a GLP-1 rector agonist in addition to the standard treatment for rectal cancer
Total neoadjuvant therapy (TNT)
Total ne-adjuvant therapy is standard treatment for locally advanced rectal cancer
Primary outcomes
Change in weight loss (Kilograms) between groups at 2 time points * Baseline * Pre TNT starting * Post TNT starting
Using a human ex vivo explant model (3D), we will assess in real time the metabolic profiles of the tissues from patents in the control and interventions groups. Detailed metabolic profiling data using Seahorse technology. These metabolic profile data will be correlated with detailed clinical, pathology and outcome data for each patient in the trial.
Using human ex vivo explant model (3D) system, we will profile the secretions of inflammatory mediators from the TME and how these cross talks to immune cells. This data will be directly correlated with the detailed metabolic signatures.
Determine of GLP-1 treatment alters mitochondrial fitness ex vivo in explants by assessing ATP levels (Relative Light Units), stress responses and adaptations to metabolic demands using tissues from both arms of the trial.
To definitively map the systemic inflammatory profile, we will investigate matched plasma samples (baseline and post-intervention) using a high dimensional approach (e.g Olink Target-96 Immunoncology panel or Olink Explore-396 inflammatory profile). Samples will be taken at the time of diagnosis and the time of surgery
Map the circulating immune system using spectral flow cytometry to include cell frequencies (e.g. T cells, Innate T cells, NK cells, Monocytes and DC subsets), activation/exhaustion phenotype (e.g. CD69, PD-1, TIM-3 etc) and cytokine profiles (e.g. interleukin (IL)-2, 4, 10 \& 17, interferon gamma, tumour necrosis factor, granzymes etc). Samples will be taken from pre treatment biopsies and from the tumour itself when removed at surgery.
Map the tumour resident immune system using MACsima spatial imaging platform and their 61- parameter immuno-oncology antibody panel (which includes T cells, NK cells, Macrophages \& DCs plus tumour specific markers). Using this platform, in addition to deep immunopheotyping, we will allow perform neighbour analysis to determine cell-cell interactions. Tissue will be taken from pre treatment biopsies and from the tumour itself when removed at surgery.
Study locations
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