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

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ClinicalTrials.gov Identifier: NCT05755672
Recruitment Status : Recruiting
First Posted : March 6, 2023
Last Update Posted : April 23, 2024
Sponsor:
Information provided by (Responsible Party):
Region Skane

Brief 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.


Condition or disease Intervention/treatment
Metastatic Colorectal Cancer Chemotherapy Effect Peritoneal Metastases Liver Metastasis Colon Cancer Lung Metastases Drug: Chemotherapy Procedure: Resection of the primary tumor Procedure: Resection of tumour metastases Procedure: Blood sampling during chemotherapy

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

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: On-treatment Biomarkers in Metastatic Colorectal Cancer for Life: The On-CALL Study
Actual Study Start Date : March 1, 2023
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : March 2033

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 Name: Surgical resection of the primary tumour

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

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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
  • Tissue from the first histological specimen for diagnosis (usually a biopsy)
  • Blood sample during ongoing neoadjuvant and/or adjuvant chemotherapy
  • Tissue from the surgical resection specimen (primary tumour and resected metastases)


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients who are treated at the Skåne University Hospital
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05755672


Contacts
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Contact: Danyil Kuznyecov, M.D. +46 725972072 danyil_szergejevics.kuznyecov@med.lu.se
Contact: Christina Siesing, M.D. PhD. +4646177841 christina.siesing@med.lu.se

Locations
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Sweden
Department of Oncology, Hematology and Radiophysics, Skane University Hospital Recruiting
Lund, Skåne, Sweden, 22241
Contact: Jakob Eberhard, M.D. PhD.    +4646177520    jakob.eberhard@med.lu.se   
Department of Oncology, Hematology and Radiophysics, Skane University Hospital Recruiting
Malmö, Skåne, Sweden, 21428
Contact: Christina Siesing, M.D. PhD.    +4646177841    christina.siesing@skane.se   
Sponsors and Collaborators
Region Skane
Investigators
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Study Director: Karin Jirström, M.D. PhD. Region Skåne
Study Chair: Jakob Eberhard, M.D. PhD. Region Skåne
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Responsible Party: Region Skane
ClinicalTrials.gov Identifier: NCT05755672    
Other Study ID Numbers: 2022-01242-01
First Posted: March 6, 2023    Key Record Dates
Last Update Posted: April 23, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Region Skane:
Metastatic colorectal cancer
Chemotherapy
Targeted therapy
Tumor heterogeneity
Tumor evolution
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes