Clinical trial NCT05674422: GEMCAD-REVEAL STUDY - Circulating Tumor DNA as a Predictor of Relapse in Patients With Locally Advanced Rectal Cancer.
Official title: Circulating Tumor DNA as a Predictor of Relapse in Patients With Locally Advanced Rectal Cancer Treated With Total Neoadjuvant Therapy Followed by Watch and Wait or Total Mesorectal Excision Based on Clinical Assessment of Response
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Patients With Locally Advanced Rectal Cancer
Keywords: rectal cancer
ctDNA
total neoadjuvant therapy
Lead sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
Sponsor class: OTHER
First posted: 2023-01-06
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with locally advanced rectal cancer candidates to TNT. All patients will be aged 18 years or older, with histologically confirmed rectal adenocarcinoma, located in the mid or distal third (with the inferior margin within 12cm from the anal verge), clinically staged II and III (cT3-T4 and/or any TN+), scheduled to undergo TNT will be eligible.

All enrolled patients will be allocated to receive TNT according to standard clinical practice.

Brief summary: The evaluation of the tumor response to chemoradiotherapy/total neoadjuvant therapy (CRT/TNT) remains a challenge. The integration of a blood-based biomarker such as ctDNA with clinico-radiological tools could offer the potential advantage of improving accuracy of assessment of tumor response to neoadjuvant therapy. Furthermore, data on functional outcomes and quality of life after total mesorectal excision (TME) and especially after " Watch And Wait" (WW) is scarce.

REVEAL is a prospective, multicenter study in which the response to TNT in correlation with liquid biopsy (LB) of patients with rectal cancer in Spain will be evaluated. It is planned to include 120 patients. All patients will be aged 18 years or older, with histologically confirmed rectal adenocarcinoma, located in the mid or distal third (with the inferior margin within 12cm from the anal verge), clinically staged II and III (cT3-T4 and/or any TN+), scheduled to undergo TNT will be eligible. All cases and treatment decisions will be discussed by local Multidisciplinary Boards. Patients will be included consecutively when visiting the corresponding health centers for outpatient visits or hospitalization.

The objective of the present study is to evaluate the role of ctDNA in the prediction of relapse in patients diagnosed with locally advanced rectal cancer (LARC) treated with TNT followed by WW or TME based on a clinical assessment of the local response

Detailed description: The evaluation of the tumor response to chemoradiotherapy/total neoadjuvant therapy (CRT/TNT) remains a challenge. The integration of a blood-based biomarker such as ctDNA with clinico-radiological tools could offer the potential advantage of improving accuracy of assessment of tumor response to neoadjuvant therapy. Furthermore, data on functional outcomes and quality of life after total mesorectal excision (TME) and especially after " Watch And Wait" (WW) is scarce.

REVEAL is a prospective, multicenter study in which the response to TNT in correlation with liquid biopsy (LB) of patients with rectal cancer in Spain will be evaluated. It is planned to include 120 patients. All patients will be aged 18 years or older, with histologically confirmed rectal adenocarcinoma, located in the mid or distal third (with the inferior margin within 12cm from the anal verge), clinically staged II and III (cT3-T4 and/or any TN+), scheduled to undergo TNT will be eligible. All cases and treatment decisions will be discussed by local Multidisciplinary Boards. Patients will be included consecutively when visiting the corresponding health centers for outpatient visits or hospitalization.

The objective of the present study is to evaluate the role of ctDNA in the prediction of relapse in patients diagnosed with locally advanced rectal cancer (LARC) treated with TNT followed by WW or TME based on a clinical assessment of the local response.

HYPOTHESIS ctDNA is a predictor of complete clinical response and could potentially be used to guide patient selection for WW strategy.

ctDNA is an early marker of local tumor relapse and could potentially guide strategy changes during follow-up.

Patients who are enrolled in a WW strategy have better long-term functional outcomes in comparison to patients who undergo surgery.

OBJECTIVES

PRIMARY:

To estimate the positive predictive value (PPV) and the negative predictive value (NPV) of the post-TNT ctDNA measurement to identify relapse (local or distant) in the 2 years after TNT.

SECONDARY:

Secondary objectives related to ctDNA and tumor response to TNT:

* To estimate the concordance between the post-TNT ctDNA measurement and the clinical evaluation of response (endoscopy-biopsy, DRE and MRI) to TNT.
* To estimate the concordance between the ctDNA measured after TNT and the endoscopy-biopsy evaluation of response.
* To estimate the concordance between the ctDNA measured after TNT and the MRI-defined response pattern groups.

Secondary objectives related to ctDNA measure during follow-up and relapse:

* To estimate the positive predictive value and the negative predictive value of ctDNA measured during the follow-up after TNT to identify relapse (local or distant) in the 2 years after TNT.
* To estimate the positive predictive value and the negative predictive value of ctDNA measured during the follow-up after TNT to identify local relapse in the 2 years after TNT
* To estimate the positive predictive value and the negative predictive value of ctDNA measured during the follow-up after TNT to identify distant relapse in the 2 years after TNT

Secondary objective related to functional impact of TME and WW:

-To describe anorectal, urinary and sexual function in the TME and WW groups.

Secondary objective related to ctDNA and survival:

-To assess the association of ctDNA levels (at baseline, post-treatment and during follow-up) with the survival outcomes (overall and disease-free survival, locoregional and distant recurrence, together with the pattern of recurrence).

Eligibility criteria: Inclusion Criteria:

* Legally capable patients ≥ 18 years of age.
* Histologically confirmed rectal adenocarcinoma.
* Any tumor located in the mid or distal rectum, clinically staged II-III (cT3/4 and/or any TN+).
* Willingness to be enrolled in the WW strategy if cCR or nCCR is achieved.
* Absence of metastases on imaging.
* Scheduled to undergo TNT followed by delayed surgery.
* Patients who have signed the informed consent for this study.

Note: Decision was taken to treat the patient with a specific treatment prior and independently of patient inclusion in this non interventional study.

Exclusion Criteria:

* Patients who do not meet inclusion criteria.
* Concomitant colorectal tumors.
* Intolerance or contraindication to planned TNT.
* Other concurrent malignant diseases. Pregnancy or breastfeeding.

Primary outcomes:
measure: ctDNA from liquid biopsy
timeFrame: 2 years after to start treatment total neoadjuvant therapy/2 years per patient
Secondary outcomes:
measure: Response to TNT (cCR,nCCR)
timeFrame: Throughout the study period, approximately 2 years per patient
measure: Response to TNT (WW or TME)
timeFrame: Throughout the study period, approximately 2 years per patient
measure: Locoregional failure rate (LRF)
timeFrame: Throughout the study period, approximately 2 years per patient
measure: Distant relapse rate (DRR)
timeFrame: Throughout the study period, approximately 2 years per patient
measure: Disease-free Survival (DFS)
timeFrame: at 1 year after the first dose of TNT and at the end of study (approximately 2 years)
measure: Disease-specific Survival (DSS)
timeFrame: at 1 year after the first dose of TNT
measure: Overall Survival (OS)
timeFrame: at 1 year after the first dose of TNT
measure: Mortality
timeFrame: Throughout the study period, approximately 2 years per patient
measure: TNT compliance
timeFrame: Throughout the study period, approximately 2 years per patient
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol - ICO Badalona
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua de Terrassa
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Comunidad Autónoma De Madrid
city: Barcelona
country: Spain
facility: H. de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: H.U. Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic, Universitat de Barcelona
city: Barcelona
country: Spain
facility: Hospital Del Mar, Barcelona
city: Barcelona
country: Spain
facility: Hospital Sant Joan Despí - Moisés Broggi.
city: Barcelona
country: Spain
facility: ICO-Hospitalet
city: Girona
country: Spain
facility: ICO Girona
city: Madrid
country: Spain
facility: H. Univeristario La Paz
city: Valencia
country: Spain
facility: Hospital Quirón Salud Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Servicio de Cirugía General y Digestiva, Hospital Clínic, Universitat de Barcelona
name: Yoelimar Guzmán, M.D.
role: STUDY_CHAIR
affiliation: Servicio de Oncología, Hospital Clínic, Universitat de Barcelona
name: Joan Maurel Santasusana, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Servicio de Radiología, Hospital Clínic, Universitat de Barcelona
name: Juan Ramón Ayuso, M.D., Ph.D.
role: STUDY_CHAIR
References: