On-treatment Biomarkers in Metastatic Colorectal Cancer for Life (On-CALL)
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| ClinicalTrials.gov Identifier: NCT05755672 |
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Recruitment Status :
Recruiting
First Posted : March 6, 2023
Last Update Posted : April 23, 2024
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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 |
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 [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 |
|---|---|
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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)
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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 |
- 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).
- 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)
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.
| 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 |
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
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
| 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 |
| 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 | |
| Study Director: | Karin Jirström, M.D. PhD. | Region Skåne | |
| Study Chair: | Jakob Eberhard, M.D. PhD. | Region Skåne |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Metastatic colorectal cancer Chemotherapy Targeted therapy Tumor heterogeneity Tumor evolution |
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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 |