On-treatment Biomarkers in Metastatic Colorectal Cancer for Life

Condition(s) studied

Investigational drug(s) / intervention(s)

Chemotherapy: Neo-adjuvant and adjuvant chemotherapy with curative intent, according to the current clinical practice guidelines

Resection of the primary tumor: Surgical resection of the primary tumour, according to the current clinical practice guidelines

Resection of tumour metastases: Surgical resection of tumour metastases, according to the current clinical practice guidelines

Blood sampling during chemotherapy: Drawing of blood samples several times during patient visits for chemotherapy regimen

Study summary

By virtue of an increased strategic use of cytotoxic and biological agents, and more options for locoregional treatment, the survival of patients with metastatic colorectal cancer (mCRC) has improved considerably in the past decades. The personalized approach to systemic treatment is further aided by the use of complementary molecular biomarkers. However, the evolutionary dynamics of mCRC, a disease harnessed by multiple adaptive genetic alterations towards its final stages, poses a particular challenge to single-sample biomarker analyses and standardized linear treatment protocols. The aim of the On-treatment biomarkers in metastatic ColorectAL cancer for Life (On-CALL) study is to generate further knowledge on the evolutionary progression of mCRC during treatment, and to elucidate the mechanisms underlying the therapeutic failure still seen in a substantial number of patients.

The On-CALL study is a prospective, single-arm observational study. All patients diagnosed with synchronous mCRC treated with curative intent at Skåne University Hospital will be invited to participate. Clinical and histopathological data will be compiled at study entry. An individual tissue microarray block with samples from resected primary tumours and metastases representing the full extent of the tumour spread will be constructed for each patient. Blood samples will be drawn for biomarker analyses at multiple time points prior to, during and after systemic treatment. DNA sequencing of tumour tissue and circulating tumour DNA (ctDNA) will be performed to define the spatial clonal landscape in primary tumours and metastases, as well as over time.

Eligibility

Primary outcome measure(s)

• Follow-up examination of tumour remission, progression or recurrence — 10 years
  Radiological/clinical examination of tumour remission, progression or recurrence, and correlation of this clinical information with the available oncogenetic data from histological samples from the primary tumour and metastases, and from data from blood samples (ctDNA analysis) * Oncogenetic data will come from genomic profiling of tissue samples. This will be carried out by targeted deep sequencing (TDS), using a comprehensive panel covering cancer-related genes, in combination with genome wide SNP array for detection of copy number aberrations. * Data from blood samples will be extracted through quantification of ctDNA and monitoring of the temporal clonal dynamics (circulating cell free DNA will be extracted from plasma samples from all time points).

Trial sites (2)

More Region Skane trials in Sweden

Other trials for the same condition