Evaluation of cfDNA as a Marker of Response in Rectal Cancer

NCT04319354 | Completed

• 1 other identifier: 85/19/56C
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer of Rectum

Keywords

rectal cancer; neoadjuvant therapy; cfDNA

Outcome Measures

Primary Outcomes (1)

• Ryan tumor regression grade system (number of patients with complete/partial/no response)

  Tumour pathological response, on surgical specimen, to neoadjuvant chemoradiotherapy

  Through study completion, an average of 1 year

Secondary Outcomes (1)

• Number of participants with 1 and 2-year disease free recurrence

  1 and 2 years

Study Arms (3)

pCR

EXPERIMENTAL

Diagnostic Test: Analysis of cfDNA

Partial responders

EXPERIMENTAL

Diagnostic Test: Analysis of cfDNA

Non-responders

ACTIVE COMPARATOR

Diagnostic Test: Analysis of cfDNA

Interventions

Analysis of cfDNA DIAGNOSTIC_TEST

Analysis of cfDNA through liquid biopsy

Non-responders; Partial responders; pCR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged over 18 years old, ECOG 0-2
• High-risk patients with biopsy proven rectal adenocarcinoma who will undergo long-course chemoradiotherapy and who are potentially eligible for curative surgery
• Patients who can fully understand the content of the informed consent form and sign it upon their own opinion
• Patients who can coordinate with the researchers to undergo the long-term post-treatment rechecks and follow-up

You may not qualify if:

• Patient has any underlying or current medical condition, which would interfere with the evaluation of the patient (e.g., end-stage liver disease, pulmonary hypertension, systemic lupus erythematosus etc.).
• Patient has severe mental illness.
• Patient has any other conditions, which would interfere with the evaluation of the subject.

Sponsors & Collaborators

• Hospital Pedro Hispano: lead
• Diogo Melo Pinto, MD, Hospital Pedro Hispano: collaborator
• Telma Fonseca, MD, Centro Hospitalar de São João: collaborator
• Silvestre Carneiro, PhD, Centro Hospitalar de São João: collaborator
• Isabel Prieto, PhD, Hospital La Paz, Madrid: collaborator

Study Sites (1)

Hospital Pedro Hispano

Matosinhos Municipality, Porto District, 4464-513, Portugal

Location

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 24, 2020
• Study Start: November 18, 2019
• Primary Completion: April 30, 2021
• Study Completion: December 30, 2021
• Last Updated: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: since the beginning, for 2 years

Locations

PT (1)