NCT04319354

Evaluation of cfDNA as a Marker of Response in Rectal Cancer

Completed NA Last updated 19 May 2023

What this trial tests

NA trial testing Analysis of cfDNA in Cancer of Rectum in 50 participants. Completed in 30 December 2021.

Timeline

18 November 2019

Primary endpoint
30 April 2021

30 December 2021

Quick facts

Lead sponsor	Hospital Pedro Hispano
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	50
Start date	18 November 2019
Primary completion	30 April 2021
Estimated completion	30 December 2021
Sites	1 location across Portugal

Drugs / interventions tested

• Analysis of cfDNA

Conditions studied

• Cancer of Rectum — all drugs for Cancer of Rectum →

Sponsor

Hospital Pedro Hispano

Who can join

18 and older, any sex, with Cancer of Rectum. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

A pathological complete response (pCR) after surgery occurs in approximately 20% of rectal cancer patients submitted to neoadjuvant chemotherapy, with apparent survival benefit. This group could, potentially, be spared the morbidity of surgery.

The diversified response to neoadjuvant chemotherapy (nCRT) amongst tumors suggests a complex relationship between tumor biology and response possibly due to a number of genetic or molecular pathways that might regulate chemoradiosensitivity.

Accumulating evidence indicated that circulating cell-free nucleic acids can be a promising biomarker of response, in liquid biopsy, for rectal cancer. The concentration of baseline plasma cell-free DNA (cfDNA) appears significantly higher in responders compared to non-responders.

The objective of this study is to investigate the potential role of cfDNA as a marker of pCR (or partial response) to nCRT as well as a marker of outcomes (overall survival and disease-free survival).

The investigators are conducting a prospective, observational, cohort, non-randomized study of consecutive patients with locally advanced rectal cancer submitted to nCRT, followed by surgical excision 6-12 weeks later. Patients are assigned to groups according to their pathological response to nCRT. A total of 20 patients with complete pathological response, 50 partial response and 50 non-responders will be selected over a year and followed for another year. Participants will be observed and examined during the entire course of treatment and the follow-up period.

Serial analysis of cfDNA through liquid biopsies will be performed in consecutive patients at specific time points (pre-nCRT, post-nCRT and postoperative week 1), incorporating analysis of concentration, dimension of DNA fragments, % of mutation frequency (CIN, APC, p53, MSI, KRAS, BRAF, EGFR, cKIT) and next-generation sequencing of tumour biopsy and surgical specimens.

This study will serve as the feasibility of a larger, comparative study.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study.
   Morais M, Fonseca T, Melo-Pinto D, Prieto I, et al · · 2023 · cited 11× · PMID 36986526 · DOI 10.3390/ph16030427
2. Exploring the clinical utility of liquid biopsy with cfDNA in cancer: A systematic review.
   Ranganathan K, Kurian NS, Goswami HM, Rishi KD, et al · · 2024 · cited 5× · PMID 40027943 · DOI 10.1016/j.jlb.2024.100150
3. Clinical Applications of Liquid Biopsy in Colorectal Cancer: A Focus on Registered Clinical Trials.
   Garcia-Pelaez J, Yáñez Y, Aupí M, Lázaro M, et al · · 2026 · PMID 42194957 · DOI 10.3390/genes17050500