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Evaluation of cfDNA as a Marker of Response in Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04319354
Recruitment Status : Recruiting
First Posted : March 24, 2020
Last Update Posted : March 24, 2020
Sponsor:
Collaborators:
Diogo Melo Pinto, MD, Hospital Pedro Hispano
Sara Rodrigues, MD, Centro Hospitalar de São João
Silvestre Carneiro, PhD, Centro Hospitalar de São João
Pedro Currais, MD, IPO Lisboa
Isadora Rosa, MD, IPO Lisboa
Isabel Prieto, PhD, Hospital La Paz, Madrid
Information provided by (Responsible Party):
Marina Morais, Hospital Pedro Hispano

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.


Condition or disease Intervention/treatment Phase
Cancer of Rectum Diagnostic Test: Analysis of cfDNA Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of cfDNA as a Marker of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2023

Arm Intervention/treatment
Experimental: pCR Diagnostic Test: Analysis of cfDNA
Analysis of cfDNA through liquid biopsy

Experimental: Partial responders Diagnostic Test: Analysis of cfDNA
Analysis of cfDNA through liquid biopsy

Active Comparator: Non-responders Diagnostic Test: Analysis of cfDNA
Analysis of cfDNA through liquid biopsy




Primary Outcome Measures :
  1. Ryan tumor regression grade system (number of patients with complete/partial/no response) [ Time Frame: Through study completion, an average of 1 year ]
    Tumour pathological response, on surgical specimen, to neoadjuvant chemoradiotherapy


Secondary Outcome Measures :
  1. Number of participants with 1 and 2-year disease free recurrence [ Time Frame: 1 and 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04319354


Contacts
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Contact: Marina Morais, MD +351910918588 morais1000@gmail.com

Locations
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Portugal
Hospital Pedro Hispano Recruiting
Matosinhos, Porto, Portugal, 4464-513
Contact: António Gouveia, PhD       antonio.mgouveia@ulsm.min-saude.pt   
Sponsors and Collaborators
Hospital Pedro Hispano
Diogo Melo Pinto, MD, Hospital Pedro Hispano
Sara Rodrigues, MD, Centro Hospitalar de São João
Silvestre Carneiro, PhD, Centro Hospitalar de São João
Pedro Currais, MD, IPO Lisboa
Isadora Rosa, MD, IPO Lisboa
Isabel Prieto, PhD, Hospital La Paz, Madrid
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Responsible Party: Marina Morais, Principal Investigator, Hospital Pedro Hispano
ClinicalTrials.gov Identifier: NCT04319354    
Other Study ID Numbers: 85/19/56C
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: March 24, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: since the beginning, for 2 years

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Marina Morais, Hospital Pedro Hispano:
rectal cancer
neoadjuvant therapy
cfDNA
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases