RECC-EV: A Prospective Feasibility Study Evaluating Extracellular Vesicles Obtained by Liquid Biopsy for Neoadjuvant Treatment Response Assessment in Rectal Cancer

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Recruiting

CT.gov ID

NCT04852653

Collaborator

(none)

Enrollment

Location

23.3

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Routine clinical and radiological assessment of response of patients with rectum cancer to neoadjuvant chemoradiotherapy does not allow accurate identification of complete pathological response, and leads to frequent false positive and negative results. Molecular markers reflecting the initial and post-nCRT status of the tumor would be ideal to select patients eligible for organ preservation. This project will test the detection of tumor extracellular vesicles (EVs) in liquid biopsy as a reliable marker for the identification of poor versus good responders to nCRT.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer Liquid Biopsy	Procedure: Supplementary blood samples collection during the normal follow up of the patients

Detailed Description

Neoadjuvant treatment (NT) followed by total mesorectum excision (TME) constitues the gold standard for locally advanced carcinoma of the low and middle rectum. When good clinical response to NT is obtain, strategies with organ preservation, including close surveillance without immediate surgery or transanal local excision, can spare patients with the highly morbid and functional cost of TME. Current assessment of good responders relies on the downstaging and/or downsizing of the tumor as evaluated by MRI imaging and clinical exam. This strategy is prone to errors in more than 1/3 cases. Better assessment of tumor response to NT would better select patients eligible for organ preservation strategies. This study will use the detection of tumor extracellular vesicles (EVs) in liquid biopsy to identify good response of rectum cancer to neoadjuvant treatment. Tumor EVs will be detected in the blood of the patients at different times of their regular management (before, during and after NT). Protein content or tumor DNA in EVs will be detected after tumor DNA sequencing in the primary biopsies. Response will be assessed according to tumor EV presence or absence in the blood. As EV quantification is possible, kinetics of their detection will help response assessment and patient follow-up.

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Prospective Feasibility Study Evaluating Extracellular Vesicles Obtained by Liquid Biopsy for Neoadjuvant Treatment Response Assessment in Rectal Cancer

Actual Study Start Date :

Sep 21, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Patients with adenocarcinoma of rectum histologically proven	Procedure: Supplementary blood samples collection during the normal follow up of the patients Supplementary blood samples collection during the normal follow up of the patients

Arm

Intervention/Treatment

Patients with adenocarcinoma of rectum histologically proven

Procedure: Supplementary blood samples collection during the normal follow up of the patients

Supplementary blood samples collection during the normal follow up of the patients

Outcome Measures

Primary Outcome Measures

Positivity of the liquid biopsy [6 months]
Presence of onco-exosomes and / or exoDNA according to the response to the neoadjuvant treatment by chemotherapy alone or followed by radiochemotherapy of rectal cancer

Secondary Outcome Measures

Prediction of the response of rectal cancer to neoadjuvant treatment [6 months]
To evaluate whether the kinetics of detection of oncoexosomes and exoDNA is a predictor of the response of rectal cancer to neoadjuvant treatment
Genetic profile of the primary tumor predictive of the response to nCRT [6 months]
To evaluate whether the initial mutational profile of the tumor is a predictor of the response of rectal cancer to chemotherapy and radiochemotherapy neoadjuvant treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adenocarcinoma of rectum histologically proven
Location ≤ 10 cm from the anal margin
Stage T3T4, or T2 if low rectal cancer
With indication of chemotherapy alone or followed by chemoradiotherapy prior to total mesorectal surgery or transanal surgery, discussed in advance at a multidisciplinary consultation meeting oncology
No metastasis
Operable patient
Patient ≥ 18 years old
Patient likely to receive radiation therapy and chemotherapy.
No history of pelvic radiotherapy for any reason, no history of chemotherapy
Effective contraception for patients of childbearing age: male and non-menopausal women must agree to use two medically validated methods of contraception (one for the patient and the other for the partner) during treatment and less up to 6 months for men and 4 months for women after last treatment
Patient information and obtaining free, informed and written consent, signed by the patient and his investigator.
Affiliate subject or beneficiary of a social security scheme of a member country of the European Community (article L1121-11 of the Code of Public Health)

Exclusion Criteria:

Tumor of the upper rectum (> 10 cm from the anal margin)
Metastatic disease

. T1 stage tumor

History of pelvic radiotherapy and chemotherapy
Contraindication to chemotherapy and / or radiotherapy

. Insufficient tumoral sample on initial rectal biopsy for performing molecular analysis of tumor by NGS.

Other concomitant cancer or history of cancer other than treated in situ cervix cancer or basal cell or squamous cell carcinoma
Pregnant woman, likely to be pregnant or breastfeeding
Symptomatic cardiac and / or coronary insufficiency
Severe renal impairment (creatinine clearance less than 30ml / min)
Full or partial deficiency in dihydropyrimidine dehydrogenase (DPD) (uracilemia ≥ 16 ng / ml)
Peripheral neuropathy> grade 1
Treatment with St. John's Wort
Treatment with yellow fever vaccine
Treatment with prophylactic phenytoin
Treatment with sorivudine or its chemically analogues related, such as brivudine
Active infection or other serious underlying disease likely to prevent the patient from receiving treatment
Persons deprived of their liberty, or under measure of judicial protection (curatorship or guardianship) or incapable of giving their consent
Impossibility of submitting to the medical follow-up of the test for geographical, social or psychological reasons.