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Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicati...

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Autores principales: Schraa, S. J., van Rooijen, K. L., van der Kruijssen, D. E. W., Rubio Alarcón, C., Phallen, J., Sausen, M., Simmons, J., Coupé, V. M. H., van Grevenstein, W. M. U., Elias, S., Verkooijen, H. M., Laclé, M. M., Bosch, L. J. W., van den Broek, D., Meijer, G. A., Velculescu, V. E., Fijneman, R. J. A., Vink, G. R., Koopman, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441668/
https://www.ncbi.nlm.nih.gov/pubmed/32819390
http://dx.doi.org/10.1186/s12885-020-07252-y
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author Schraa, S. J.
van Rooijen, K. L.
van der Kruijssen, D. E. W.
Rubio Alarcón, C.
Phallen, J.
Sausen, M.
Simmons, J.
Coupé, V. M. H.
van Grevenstein, W. M. U.
Elias, S.
Verkooijen, H. M.
Laclé, M. M.
Bosch, L. J. W.
van den Broek, D.
Meijer, G. A.
Velculescu, V. E.
Fijneman, R. J. A.
Vink, G. R.
Koopman, M.
author_facet Schraa, S. J.
van Rooijen, K. L.
van der Kruijssen, D. E. W.
Rubio Alarcón, C.
Phallen, J.
Sausen, M.
Simmons, J.
Coupé, V. M. H.
van Grevenstein, W. M. U.
Elias, S.
Verkooijen, H. M.
Laclé, M. M.
Bosch, L. J. W.
van den Broek, D.
Meijer, G. A.
Velculescu, V. E.
Fijneman, R. J. A.
Vink, G. R.
Koopman, M.
author_sort Schraa, S. J.
collection PubMed
description BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the ‘trial within cohorts’ (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281
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spelling pubmed-74416682020-08-24 Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study Schraa, S. J. van Rooijen, K. L. van der Kruijssen, D. E. W. Rubio Alarcón, C. Phallen, J. Sausen, M. Simmons, J. Coupé, V. M. H. van Grevenstein, W. M. U. Elias, S. Verkooijen, H. M. Laclé, M. M. Bosch, L. J. W. van den Broek, D. Meijer, G. A. Velculescu, V. E. Fijneman, R. J. A. Vink, G. R. Koopman, M. BMC Cancer Study Protocol BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the ‘trial within cohorts’ (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281 BioMed Central 2020-08-20 /pmc/articles/PMC7441668/ /pubmed/32819390 http://dx.doi.org/10.1186/s12885-020-07252-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Schraa, S. J.
van Rooijen, K. L.
van der Kruijssen, D. E. W.
Rubio Alarcón, C.
Phallen, J.
Sausen, M.
Simmons, J.
Coupé, V. M. H.
van Grevenstein, W. M. U.
Elias, S.
Verkooijen, H. M.
Laclé, M. M.
Bosch, L. J. W.
van den Broek, D.
Meijer, G. A.
Velculescu, V. E.
Fijneman, R. J. A.
Vink, G. R.
Koopman, M.
Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title_full Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title_fullStr Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title_full_unstemmed Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title_short Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study
title_sort circulating tumor dna guided adjuvant chemotherapy in stage ii colon cancer (medocc-create): study protocol for a trial within a cohort study
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441668/
https://www.ncbi.nlm.nih.gov/pubmed/32819390
http://dx.doi.org/10.1186/s12885-020-07252-y
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