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NCT Number: NCT06831669

Metabolomics to Predict Treatment Response and Toxicities in Rectal Cancer

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.

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Key information

Conditions

Rectal Neoplasm Malignant Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

20 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

Hypothesis: Metabolomic profiling can be used to predict the response to total neoadjuvant therapy (TNT) and the incidence of radiotherapy-related diarrhoea in patients with locally advanced rectal cancer.

Rationale of the project: Metabolomics is a powerful tool for identifying biomarkers that are associated with disease and treatment response. It is more closely related to the biological phenotype than other omics approaches, such as genomics and transcriptomics, and it has the potential to be used for precision health applications.

In this project, the investigators aim to use metabolomics to predict the response to total neoadjuvant therapy (TNT) and the incidence of treatment-related toxicity in rectal cancer patients prior to treatment. This would allow us to select patients who are most likely to benefit from TNT and to minimize the risk of complications.

There is a growing body of evidence that suggests that metabolomics can be used to predict treatment response and toxicity in cancer patients. For example, one study found that plasma metabolites could be used to predict the overall survival and progression-free survival of patients with colorectal cancer. Another study found that the level of pretreatment faecal butyrate was directly related to gastrointestinal toxicity in prostate cancer patients. However, most studies on metabolomics and cancer have used long-course chemoradiotherapy. There is a limited amount of research on the use of metabolomics to predict treatment response and toxicity to TNT.

This project is the first to comprehensively evaluate the metabolomic profiles of patients with locally advanced rectal cancer undergoing TNT at multiple time points during and after treatment using liquid chromatography-mass spectrometry (LC-MS), and to assess the association of these profiles with treatment response and toxicities. The findings from this study have the potential to lead to the development of non-invasive biomarkers for predicting treatment response and toxicities, which could improve the clinical management of rectal cancer patients.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed adenocarcinoma of the rectum
  • Scheduled to receive total neoadjuvant therapy

Exclusion criteria

  • Previous pelvic radiation therapy
  • Inflammatory bowel disease

Treatment and study plan

Collecting biospecimens

Other

Collecting blood, urine, tissue, and faecal samples

Primary outcomes

  1. Predictive Accuracy of Metabolomic Profiles for Complete Response (CR)

    Time frame: From enrollment to surgical resection or up to 6 months after completion of radiotherapy (whichever occurs first)

    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.

Secondary outcomes

  1. Number of Participants With Grade 3-4 Treatment-Related Toxicities as Assessed by CTCAE

    Time frame: From initiation of radiotherapy to 21 days after completion.

    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).

Other outcomes

  1. Changes in Metabolomic Profiles From Baseline to Post-Radiotherapy

    Time frame: At baseline, and within two weeks and three months following completion of 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.

  2. Correlation Between Changes in Metabolomic Biomarkers and Grade 3-4 Toxicities

    Time frame: From baseline to 21 days after completion of radiotherapy.

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Eric Yi-Liang Shen, PhD

CONTACT

[email protected]

0975366392

Yu-Hsien Chou, MS

CONTACT

[email protected]

+886-935667922

Sponsors and collaborators

Lead sponsor

Chang Gung Memorial Hospital

Other

Registry information

Official study title

Metabolomic Profiles as Predictors of Treatment Response and Toxicities in Locally Advanced Rectal Cancer Undergoing Total Neoadjuvant Therapy

Important dates

Study start
2024
Primary completion
2028
Study completion
2033
First posted
Feb 18, 2025
Registry last updated
Apr 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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