Relapse Markers for Colorectal Cancer

Study Overview
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Brief Summary
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This is an observational case-control study which enroll metastatic and non-metastatic colorectal cancer (CRC) patients. The objective of this study is to evaluate a novel blood multi-marker test for the detection of relapse in colorectal cancer patients. This test is based on whole-blood transcriptomic signatures and circulating tumor methylated DNA markers. The patients will be enrolled into 4 study groups, two cross-sectional and two longitudinal groups, to follow up patients up to 36 months from primary tumor resection.

Official Title
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Evaluation of a Novel Blood Multi-marker Test for the Detection of Colorectal Cancer Relapse

Conditions
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Colorectal Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age at time of informed consent. Subject has signed the informed consent form (ICF) and is able to understand the information provided in it. At least a blood sample is collected per subject according to the sample collection protocol. Patients enrolled in local prospective protocols, in which samples have been collected according the study procedures may be included. Group 1: patients with a radiologically and, whenever is possible, histologically confirmed relapse (local or distant) of colorectal cancer within 5 years from primary surgery. Metachronous primary tumors are not considered as relapse and should be excluded. Group 2: Patients declared disease-free for at least 36 months but less than 5 years, as confirmed by radiological examination. Group 3: Patients with a stage III-IV colorectal cancer with a curative treatment and disease-free for at least 3 months but less than 18 months. Group 4: Histologically and radiologically confirmed diagnosis of stage I, II, III or IV colorectal adenocarcinoma, eligible for a treatment with curative intent. Exclusion Criteria: Personal history of cancer (non-hematologic) other than CRC in complete remission for less than 5 years. Personal history of hematologic cancer. A blood transfusion within 6 weeks prior to inclusion into the study. Transplant with regular intake of immunosuppressants. Pregnant woman (self-declaration). Conditions or comorbidities that would preclude the compliance with the planned surveillance program or with the protocol as judged by the Investigator. Previous inclusion in the RELMA-C study and/or re-inclusion in a different study group. Group 1: Any treatment for CRC relapse prior to blood collection. Group 2: Patient is disease-free for less than 36 months or more than 5 years. Group 3: Patient is disease-free for less than 3 months or more than 18 months Group 3: Stage IV patients with detectable residual disease after primary treatment. Group 4: Any cancer treatment prior to blood collection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| G1, CRC Relapse<br>Patients with an actual relapse of CRC, within 5 years from primary surgery. A single blood sample is collected at relapse diagnosis. | |
| G2, CRC Disease-free<br>Patients previously diagnosed with CRC and declared disease-free for at least 36 months but less than 5 years. A single blood sample is collected at standard monitoring visit. | |
| G3, CRC Disease-free (longitudinal)<br>Patients declared disease-free for at least 3 months but less than 18 months. Longitudinal blood samples will be collected during standard monitoring visits up to relapse, or for a maximum of 4 time points. | |
| G4, Primary CRC (longitudinal)<br>Patients with an actual diagnosis of CRC who are eligible for a treatment with curative intent. Blood samples will be collected pre and post-surgery ( 6 weeks) and, eventually, at relapse. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity for relapse detection | Sensitivity of the test for detection of CRC relapse using radiological imaging as the reference diagnostic method | Relapse occurring within 5 years from primary curative intervention | 
| Specificity for relapse detection | Specificity of the test for detection of CRC relapse using radiological imaging as the reference diagnostic method | 36 months disease-free | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance analyses | Concordance analyses between the multi-marker and Carcinoembryonic Antigen (CEA) test for all patients and time points | 24 months | 
| Test positivity | Estimation of the multi-marker test positivity for all patients and time points | 24 months | 
| Coefficient of variation of the biomarkers | Intra- and inter-individual coefficient of variation of the biomarkers, pre- and post-surgery and during surveillance up to relapse | 6 weeks | 
| Sensitivity for CRC detection | Sensitivity of the test for detection of primary CRC | up to 1 day prior to tumor resection |