On-treatment Biomarkers in Metastatic Colorectal Cancer for Life (On-CALL)

April 22, 2024 updated by: Region Skane

On-treatment Biomarkers in Metastatic Colorectal Cancer for Life: The On-CALL Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 with curative intent, and to elucidate the mechanisms underlying the therapeutic failure still seen in a substantial number of patients.

The specific objectives are:

  • To comprehensively characterise the spatial intertumoural, intermetastatic and intrametastatic genetic heterogeneity
  • To delineate differences in the prevalence and type of genetic heterogeneity, as well as tumour evolvability, according to metastatic site
  • To examine the associations between spatial and temporal heterogeneity
  • To examine ctDNA quantity and quality as an early biomarker for response to neoadjuvant treatment
  • To examine ctDNA quantity and quality as an early biomarker for response to adjuvant treatment
  • To evaluate the relationship between phylogenetic patterns, i.e. the tumour evolvability, and survival in relation to different treatment modalities
  • To examine the heterogeneity of the tumour microenvironment in relation to the genetic heterogeneity and evolvability of the tumours
  • To examine circulating immune cells and inflammatory biomarkers, and their relationship with the genetic and microenvironmental heterogeneity of the tumours
  • To delineate parallel events at the transcriptomic and proteomic levels, with particular reference to their potential utility as clinically relevant surrogate biomarkers of genetic alterations underlying the evolvability of the tumours

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Sweden
    • Skåne
      • Lund, Skåne, Sweden, 22241
        • Recruiting
        • Department of Oncology, Hematology and Radiophysics, Skane University Hospital
        • Contact:
      • Malmö, Skåne, Sweden, 21428
        • Recruiting
        • Department of Oncology, Hematology and Radiophysics, Skane University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All patients who are treated at the Skåne University Hospital

Description

Inclusion Criteria:

  • Clinical diagnosis of synchronous metastatic colorectal cancer, planned cancer treatment with curative intent at the Skåne University Hospital

Exclusion Criteria:

  • Not accepting the study inclusion terms (informed consent not obtained)
  • Age below or above the age limit

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Synchronous mCRC patients
Patients diagnosed with synchronous metastatic colorectal cancer with planned treatment with curative intent at Skåne University Hospital (Malmö and Lund), who have accepted the study invitation (agreeing to participation - informed consent)
Drug: Chemotherapy
Neo-adjuvant and adjuvant chemotherapy with curative intent, according to the current clinical practice guidelines
Procedure: Resection of the primary tumor
Surgical resection of the primary tumour, according to the current clinical practice guidelines
Other Names:
  • Surgical resection of the primary tumour
Procedure: Resection of tumour metastases
Surgical resection of tumour metastases, according to the current clinical practice guidelines
Other Names:
  • Surgical resection of tumour metastases
Procedure: Blood sampling during chemotherapy
Drawing of blood samples several times during patient visits for chemotherapy regimen
Other Names:
  • Drawing of blood samples during chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Follow-up examination of tumour remission, progression or recurrence
Time Frame: 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).
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life changes
Time Frame: 10 years

Patients will take quality-of-life surveys (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - version EORTC-QLQ-C30 and EORTC-QLQ-CR29) will assistance of medical professionals prior to and after neoadjuvant and/or adjuvant treatment.

  • These surveys are cancer-specific core questionnaires for use in relation to various cancers.
  • The questionnaire scales the items on a score of 1 (Not at all) to 4 (Very much), and 1 (Very poor) to 7 (Excellent).
  • Scoring result is 0 to 100; for functional and global quality of life scales, higher scores mean a better level of functioning, and for symptom-oriented scales, a higher score means worse/more severe symptoms.
  • Statistical analysis will be performed with the data from the questionnaires, and the evolution/changes of symptoms and subjective experiences of the patients will be quantified and correlated with the clinical findings.
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Skane

Investigators

  • Study Director: Karin Jirström, M.D. PhD., Region Skane
  • Study Chair: Jakob Eberhard, M.D. PhD., Region Skane

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2033

Study Registration Dates

First Submitted

February 17, 2023

First Submitted That Met QC Criteria

March 2, 2023

First Posted (Actual)

March 6, 2023

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-01242-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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