Observational Study on Rectal Cancer to Verify if Response After Chemo-radiotherapy Can be Predicted With a Particular Blood Test. (LiBReCa)

• ClinicalTrials.gov Identifier: NCT03699410
• Recruitment Status: Terminated
• First Posted: October 9, 2018
• Last Update Posted: October 13, 2021
• Sponsor: Dimitri Christoforidis
• Collaborator: Clinical Trial Unit Ente Ospedaliero Cantonale
• Information provided by (Responsible Party): Dimitri Christoforidis, Ente Ospedaliero Cantonale, Bellinzona

Study Description

Brief Summary:

Research project for patients with locally advanced rectal cancer in which biological material and health-related personal data are collected.

The aim is to investigate if an additional method (liquid biopsies) can predict the response after chemo-radiotherapy and before surgery.

Condition or disease	Intervention/treatment
Locally Advanced Rectal Cancer	Radiation: Neoadjuvant radiotherapy; Drug: Neoadjuvant chemotherapy; Procedure: Radical surgery

Detailed Description:

The standard treatment for locally advanced rectal cancer (T3 -T4 and / or N+) is neoadjuvant (pre-operative) chemo-radiotherapy (nCRT) followed by radical surgery. In patients after complete response following nCRT, surgery may not add any survival benefit but it is still performed.

Since clinical complete response has only partial concordance with pathological complete response, an additional method that helps identify those patients with a true complete response is needed to avoid unnecessary surgery and its associated potential complications..

The hypothesis underlying this study is that the quantitative and qualitative evaluation of circulating tumor DNA (ctDNA) of liquid biopsy, based on the amount of ctDNA or on the detection of specific gene alterations respectively, may be directly correlated to the clinical, histopathological and radiological response of the tumor to nCRT.

This study will not interfere with the patient's routine treatment pathway and there will be no deviation from the standard of care. The only additional study intervention will be the collection of blood samples at 6 different time points which can be combined with the regular blood examination performed during the treatment.

At the time of diagnosis, tumor staging and histopathology on tumor biopsy will be performed. Patients will receive standardized neoadjuvant therapy and will be operated after an observational period of 10 weeks. Peripheral blood sample will be collected at 6 time points: pre-nCRT, at the end of the nCRT, at 4th and 7th week post-CRT, on the day of the surgery (before surgical resection), on the post-operative day 5 (in hospital). Mesenteric blood sample will be collected intra-operatively on the day of the surgery. Tumor sampling will be performed during tumor staging, as standard of care, and on the resection specimen. A combined qualitative and quantitative approach for the molecular characterization of tissue and liquid biopsy using next-generation sequencing will be carried out.

Study Design

• Study Type: Observational
• Actual Enrollment: 25 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: A Proof-of-concept, Prospective, Observational Study to Investigate the Value of Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-radiotherapy in Patients With Locally Advanced Rectal Cancer: the LiBReCa Study
• Actual Study Start Date: August 28, 2018
• Actual Primary Completion Date: October 20, 2020
• Actual Study Completion Date: October 20, 2020

Groups and Cohorts

Intervention Details:

• Radiation: Neoadjuvant radiotherapy
  Radiotherapy with total dose of at least 50 Gy on the tumor (cT) and the involved nodes (cN+) and with standard fractionation (1.8 Gy/fraction), 5 days/week.
• Drug: Neoadjuvant chemotherapy
  Oral Capecitabine, at the standard dose of 825 mg/m2 twice daily, concomitant to radiotherapy.
• Procedure: Radical surgery
  The time point of surgery is usually dependent on surgeon's and institutional habits and lies within 6 to 12 weeks after the end of nCRT. Surgeons participating in this study will be asked to operate patients on the 10th week after the end of nCRT.

Outcome Measures

Primary Outcome Measures :

1. Negative Prognostic Value (NPV) [ Time Frame: day of surgery ]
   NPV of the liquid biopsy of ctDNA drawn from the mesenteric and peripheral blood

Biospecimen Retention:   Samples With DNA

Tissue: the biopsy at the time of diagnosis will be characterized using next-generation sequencing (NGS).

Blood: circulating tumor DNAs (ctDNAs) from plasma collected at diagnosis and at various time-points in the patients' treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with locally advanced rectal cancer afferent to participating sites

Criteria

Inclusion Criteria:

• Age ≥ 18 years old
• Locally advanced rectal cancer (T3 or T4, and/or N+) requiring long course nCRT (as decided by the regional tumor board)
• Patient fit for surgery and treated with curative intent
• Willingness to complete all clinical and radiological examinations foreseen by the study
• Availability of tissue specimen for molecular characterization at baseline
• Written informed consent

Exclusion Criteria:

• Presence of metastases
• Insufficient material on the tissue biopsy to be left in archives of the Cantonal Institute of Pathology for further evaluations/analyses
• Insufficient amount of tumor cells in the tissue biopsy for the molecular characterization
• Inability to consent and follow the procedures of the study
• Women who are pregnant or breast feeding

Contacts and Locations

Locations

Switzerland

Regional Hospital of Lugano

Lugano, Switzerland, 6900

Clinica Luganese Moncucco

Lugano, Switzerland, 6903

Sponsors and Collaborators

Dimitri Christoforidis

Clinical Trial Unit Ente Ospedaliero Cantonale

Investigators

• Principal Investigator: Dimitri Christoforidis; Surgery and Visceral Surgery Departments Regional Hospital of Lugano

More Information

• Responsible Party: Dimitri Christoforidis, Deputy Chief of the Surgery and Visceral Surgery Departments, Ente Ospedaliero Cantonale, Bellinzona
• ClinicalTrials.gov Identifier: NCT03699410
• Other Study ID Numbers: ORL-CHIR-002
• First Posted: October 9, 2018
• Last Update Posted: October 13, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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