Evaluation of cfDNA as a Marker of Response in Rectal Cancer

NCT ID: NCT04319354

Last Updated: 2023-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-18
• Study Completion Date: 2021-12-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

pCR

Group Type: EXPERIMENTAL

Analysis of cfDNA

Intervention Type: DIAGNOSTIC_TEST

Analysis of cfDNA through liquid biopsy

Partial responders

Group Type: EXPERIMENTAL

Analysis of cfDNA

Intervention Type: DIAGNOSTIC_TEST

Analysis of cfDNA through liquid biopsy

Non-responders

Group Type: ACTIVE_COMPARATOR

Analysis of cfDNA

Intervention Type: DIAGNOSTIC_TEST

Analysis of cfDNA through liquid biopsy

Interventions

Analysis of cfDNA

Analysis of cfDNA through liquid biopsy

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Patients aged over 18 years old, ECOG 0-2

2. High-risk patients with biopsy proven rectal adenocarcinoma who will undergo long-course chemoradiotherapy and who are potentially eligible for curative surgery

3. Patients who can fully understand the content of the informed consent form and sign it upon their own opinion

4. Patients who can coordinate with the researchers to undergo the long-term post-treatment rechecks and follow-up

Exclusion Criteria

1. 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.).

2. Patient has severe mental illness.

3. Patient has any other conditions, which would interfere with the evaluation of the subject.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Diogo Melo Pinto, MD, Hospital Pedro Hispano

UNKNOWN

Sponsor Role: collaborator

Telma Fonseca, MD, Centro Hospitalar de São João

UNKNOWN

Sponsor Role: collaborator

Silvestre Carneiro, PhD, Centro Hospitalar de São João

UNKNOWN

Sponsor Role: collaborator

Isabel Prieto, PhD, Hospital La Paz, Madrid

UNKNOWN

Sponsor Role: collaborator

Hospital Pedro Hispano

OTHER

Sponsor Role: lead

Responsible Party

Marina Morais

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital Pedro Hispano

Matosinhos Municipality, Porto District, Portugal

Countries

Portugal

Other Identifiers

85/19/56C

Identifier Type: -

Identifier Source: org_study_id