Metabolomics to Predict Treatment Response and Toxicities in Rectal Cancer
ConditionRectal Neoplasm Malignant
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age20+
SponsorChang Gung Memorial Hospital
About this trial
Background: Colorectal cancer is the leading cause of cancer-related deaths in Taiwan, with rectal cancer accounting for approximately 27% of all cases. Total neoadjuvant therapy (TNT), which consists of chemotherapy and radiation therapy delivered before surgery, has become the standard of care for locally advanced rectal cancer. However, there is currently no reliable method for predicting the response to TNT or the occurrence of radiation proctitis, a common side effect of treatment.
Objective: This study aims to evaluate the metabolomic profiles of individuals with locally advanced rectal cancer undergoing TNT and to identify a panel of metabolites that can predict treatment response and toxicities.
Methods: A prospective cohort study will be conducted to enrol patients with locally advanced rectal cancer who are scheduled to receive TNT. Blood, urine, tissue, and faecal samples will be collected at baseline, during, and after chemoradiotherapy. Metabolomic profiling of the samples will be performed using liquid-chromatography mass spectrometry (LC-MS). Treatment response will be assessed based on clinical downstaging (defined as a decrease in tumour size and/or T and N stage after TNT) and pathological response, such as pathological complete response (pCR). Radiation proctitis will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. PCA and PLSDA will be used to identify metabolites that are associated with treatment response and radiation proctitis. Receiver operating characteristic (ROC) curves will be used to assess the predictive performance of the identified metabolites. Univariate and multivariate logistic regression will be used to build models to predict treatment response and radiation proctitis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed adenocarcinoma of the rectum
Scheduled to receive total neoadjuvant therapy
Disqualifiers
Previous pelvic radiation therapy
Inflammatory bowel disease
Trial population
This study will prospectively recruit 250 patients with locally advanced rectal cancer who are scheduled to receive total neoadjuvant therapy (TNT) at Chang Gung Memorial Hospital, Linkou, over a two-year period from 2024 to 2025. Blood, urine, fecal, and tissue samples will be collected from patients at baseline, during, and after TNT.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Collecting biospecimens
Other interventionCollecting blood, urine, tissue, and faecal samples
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Predictive Accuracy of Metabolomic Profiles for Complete Response (CR)
Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of metabolomic signatures in predicting complete response (CR). For patients undergoing surgical resection, CR will be determined based on histopathological examination of resected specimens (pathological CR). For patients who do not undergo surgery, clinical CR will be defined by findings from digital rectal examination (DRE), colonoscopy, and imaging studies (e.g., MRI or CT) up to six months after radiotherapy completion.
Time frame
From enrollment to surgical resection or up to 6 months after completion of radiotherapy (whichever occurs first)Secondary outcomes
1
Number of Participants With Grade 3-4 Treatment-Related Toxicities as Assessed by CTCAE
Incidence of severe (Grade 3-4) toxicities associated with radiotherapy, as determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 5.0).
Time frame
From initiation of radiotherapy to 21 days after completion.Other outcomes
1
Changes in Metabolomic Profiles From Baseline to Post-Radiotherapy
Alterations in identified metabolomic biomarkers (e.g., normalised intensities of specific metabolites measured by LC-MS) between baseline and post-radiotherapy time points. Reported as changes in metabolite intensities (e.g., mean, median, or fold change) compared to baseline measurements.
Time frame
At baseline, and within two weeks and three months following completion of radiotherapy.2
Correlation Between Changes in Metabolomic Biomarkers and Grade 3-4 Toxicities
Correlation (e.g., Pearson's or Spearman's correlation coefficient) between alterations in metabolomic profiles and the incidence of Grade 3-4 toxicities during and immediately following radiotherapy.
Time frame
From baseline to 21 days after completion of radiotherapy.Sponsors and contacts
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Source ClinicalTrials.gov