On-treatment biomarkers in metastatic ColorectAL cancer for Life (On-CALL)

The On-CALL study is a prospective, single-arm observational study. ClinicalTrials.gov Identifier: NCT05755672.
All patients with synchronous mCRC (adenocarcinoma) treated with curative intent at Skåne University Hospital will be invited to participate. Eligible patients will be identified at a weekly multidisciplinary tumor board meeting. Before start of treatment, the patients will receive information about the study by a physician and give their written informed consent. Clinical and histopathological data will be compiled at study entry. Radiological and clinical follow ups will be conducted when deemed necessary by the clinician. Primary endpoint is OS, secondary endpoints are disease specific survival and change in quality of life. Tumor tissue will be obtained from the surgical specimens, predominantly from formalin-fixed paraffin embedded (FFPE) tissue, and in some cases, fresh tissue will also be obtained at surgery for cryopreservation to enable further in-depth multi-omic approaches and future preclinical studies. All blood samples will be taken in conjunction with the treatment visits. In patients who do not receive neoadjuvant treatment, the pre-intervention sample will be taken prior to surgery. The end of treatment sample will be taken at the follow-up visit, usually at the oncology department. Quality-of-life surveys (EORTC-QLQ-C30) will be taken prior to and after neoadjuvant and/or adjuvant treatment. The first patient was enrolled in February 2023, and a total enrolment of 100 patients is planned.

The overarching aim of the On-CALL study is to generate further knowledge on the evolutionary progression of metastatic colorectal cancer during treatment with curative intent, and to elucidate the mechanisms underlying the therapeutic failure still seen in a substantial number of patients.

Specific aims:
•To evaluate the associations between phylogenetic patterns, as a measure for tumor evolvability, and survival in relation to different treatment modalities.
•To delineate spatial and temporal dynamic patterns of different immune cell subsets during systemic chemotherapy down to the single cell level, with particular reference to how these patterns align with genetic tumor evolution and patient outcome.
•To examine the interactions of different immune cell subsets with tumor cells and the tumor stroma in primary and metastatic tumor tissue obtained from surgically resected specimens.
•To delineate parallel events at the proteomic level in tissue and blood, and to identify clinically relevant surrogate biomarkers of genetic alterations underlying the evolvability of the tumors.
•To identify biomarkers for improved prediction of the occurrence, severity and responsiveness to medications of common symptoms associated with the disease and its treatment such as pain, fatigue, sleep disturbance and depression.

On-CALL är en observationsstudie för patienter med cancer i tjock- eller ändtarmen med samtidig spridning (metastaser) till andra organ, där sjukdomen har bedömts som potentiellt botbar. Målet med studien är att identifiera och jämföra biologiska egenskaper hos modertumören och metastaserna, som har betydelse för effekten av olika typer av behandlingar såsom cellgifter och/eller målriktade antikroppar, som ges i kombination med kirurgisk behandling. Vår förhoppning är att resultaten ska hjälpa oss att ta fram nya analysmetoder som gör att vi i framtiden bättre kan förutspå vilken typ av behandling som har bäst effekt hos enskilda patienter. De tumöregenskaper som ska undersökas är bl a DNA-förändringar och olika proteiner i tumörcellerna, samt immunceller och andra typer av celler i stödjevävnaden omkring tumören. Vi kommer också att undersöka förekomsten av tumör-DNA, olika proteiner samt immunceller i blodprov som tas i samband med behandling.