Clinical trial · Interventional
Evaluating the Impact of GLP-1 Receptor Agonists With Total Neoadjuvant Therapy in Rectal Cancer
A Phase II Multi-institutional Randomized Trial Evaluating the Impact of GLP-1 Receptor Agonists in Combination With Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| GLP-1 | — | UNRESOLVED | — |
| Locally Advanced Rectal Cancer (LARC) | Malignant Rectal Neoplasm | CURATED_BROADER | 0.78 |
| Obesity &Amp; Overweight | — | UNRESOLVED | — |
| Rectal Cancer Patients | — | UNRESOLVED | — |
| Total Neoadjuvant Therapy | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| GLP-1 receptor agonist | Drug | — | UNRESOLVED |
| Total neoadjuvant therapy (TNT) | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Total Neoadjuvant Therapy and GLP-1 Receptor Agonist
- description
- This arm will have patients with increased BMI and locally advanced rectal cancer having total neoadjuvant chemoradiotherapy. This arm will be given a GLP-1 receptor agonist
- interventionNames
- Drug: GLP-1 receptor agonist
- Drug: Total neoadjuvant therapy (TNT)
- type
- ACTIVE_COMPARATOR
- label
- Locally advanced rectal cancer and total neoadjuvant therapy alone
- description
- Patients with a high BMI and locally advanced rectal cancer undergoing total neoadjuvant therapy with not receiving a GLP-1 receptor agonist
- interventionNames
- Drug: Total neoadjuvant therapy (TNT)
Primary outcomes (7)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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 * Imaging available for radiomics analysis * Absence of metastatic disease at registration. * Adequate renal function is defined as calculated creatinine clearance (CrCl) \>50ml/min. * ANC \> 1.5 cells/mm3, HGB \> 8.0 gm/dl, PLT \> 150,000/mm3, total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's Syndrome who must have total bilirubin ≤ 3.0 x ULN), AST≤ 3 x ULN, ALT ≤ 3 x ULN * Able to tolerate medication. * ECOG 0-2 Exclusion Criteria: * 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 * Metastatic disease at presentation * Patients unable to undergo MRI * Patients having already received weight-loss intervention (pharmacological or surgical)
References
Publications (13)
- RESULTKazi T, McKechnie T, Lee Y, Alsayari R, Talwar G, Doumouras A, Hong D, Eskicioglu C. The impact of obesity on postoperative outcomes following surgery for colorectal cancer: analysis of the National Inpatient Sample 2015-2019. ANZ J Surg. 2024 Jul-Aug;94(7-8):1305-1312. doi: 10.1111/ans.19135. Epub 2024 Jun 18. PMID 38888262
- RESULTMartin-Carnicero A, Ramalle-Gomara E, Rubio-Mediavilla S, Alonso-Lago M, Zorrilla-Larraga M, Manrique-Abos I, de Las Heras-Duena ME, Larrayoz IM, Martinez A. Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy. J Clin Med. 2022 Oct 16;11(20):6091. doi: 10.3390/jcm11206091. PMID 36294412
- RESULTDizdarevic E, Hansen TF, Jakobsen A. The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal. Cancers (Basel). 2022 Apr 30;14(9):2252. doi: 10.3390/cancers14092252. PMID 35565381
- RESULTChen C, Douglas MP, Ragavan MV, Phillips KA, Jansen JP. Clinical Validity and Utility of Circulating Tumor DNA (ctDNA) Testing in Advanced Non-small Cell Lung Cancer (aNSCLC): A Systematic Literature Review and Meta-analysis. Mol Diagn Ther. 2024 Sep;28(5):525-536. doi: 10.1007/s40291-024-00725-x. Epub 2024 Aug 2. PMID 39093546
- RESULTRyan EJ, Creavin B, Sheahan K. Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm. Front Oncol. 2020 Aug 14;10:1369. doi: 10.3389/fonc.2020.01369. eCollection 2020. PMID 32923389
- RESULTSilverii GA, Marinelli C, Bettarini C, Del Vescovo GG, Monami M, Mannucci E. GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2025 Aug;27(8):4454-4468. doi: 10.1111/dom.16489. Epub 2025 May 29. PMID 40437949