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

S. J. Schraa; K. L. van Rooijen; D. E. W. van der Kruijssen; C. Rubio Alarcon; J. Phallen; M. Sausen; J. Simmons; V. M. H. Coupe; W. M. U. van Grevenstein; S. Elias; H. M. Verkooijen; M. M. Lacle; L. J. W. Bosch; D. van den Broek; G. A. Meijer; V. E. Velculescu; R. J. A. Fijneman; G. R. Vink; M. Koopman; Liselot van Iersel; PLCRC-MEDOCC group

doi:10.1186/s12885-020-07252-y

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

S. J. Schraa, K. L. van Rooijen, D. E. W. van der Kruijssen, C. Rubio Alarcon, J. Phallen, M. Sausen, J. Simmons, V. M. H. Coupe, W. M. U. van Grevenstein, S. Elias, H. M. Verkooijen, M. M. Lacle, L. J. W. Bosch, D. van den Broek, G. A. Meijer, V. E. Velculescu, R. J. A. Fijneman, G. R. Vink, M. Koopman^*, Liselot van IerselPLCRC-MEDOCC group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

23 Citations (Web of Science)

Abstract

BackgroundAccurate 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/designMEDOCC-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 (TM) platform. Patients with detectable ctDNA will be offered ACT consisting of 8cycles 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.DiscussionThe 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 registrationNetherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281

Original language	English
Article number	790
Number of pages	10
Journal	BMC Cancer
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12885-020-07252-y
Publication status	Published - 20 Aug 2020

Keywords

Colon cancer
Circulating tumor DNA
ctDNA
Adjuvant chemotherapy
TwiCs
RANDOMIZED CONTROLLED-TRIAL
CELL-FREE DNA
COLORECTAL-CANCER
RESIDUAL DISEASE
FLUOROURACIL
RECURRENCE
SURVIVAL
LEUCOVORIN
RISK
OXALIPLATIN

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Schraa, S. J., van Rooijen, K. L., van der Kruijssen, D. E. W., Alarcon, C. R., Phallen, J., Sausen, M., Simmons, J., Coupe, V. M. H., van Grevenstein, W. M. U., Elias, S., Verkooijen, H. M., Lacle, 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., ... PLCRC-MEDOCC group (2020). Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study. BMC Cancer, 20(1), Article 790. https://doi.org/10.1186/s12885-020-07252-y

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

abstract = "BackgroundAccurate 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/designMEDOCC-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 (TM) platform. Patients with detectable ctDNA will be offered ACT consisting of 8cycles 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.DiscussionThe 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 registrationNetherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281",

keywords = "Colon cancer, Circulating tumor DNA, ctDNA, Adjuvant chemotherapy, TwiCs, RANDOMIZED CONTROLLED-TRIAL, CELL-FREE DNA, COLORECTAL-CANCER, RESIDUAL DISEASE, FLUOROURACIL, RECURRENCE, SURVIVAL, LEUCOVORIN, RISK, OXALIPLATIN",

author = "Schraa, {S. J.} and {van Rooijen}, {K. L.} and {van der Kruijssen}, {D. E. W.} and Alarcon, {C. Rubio} and J. Phallen and M. Sausen and J. Simmons and Coupe, {V. M. H.} and {van Grevenstein}, {W. M. U.} and S. Elias and Verkooijen, {H. M.} and Lacle, {M. M.} and Bosch, {L. J. W.} and {van den Broek}, D. and Meijer, {G. A.} and Velculescu, {V. E.} and Fijneman, {R. J. A.} and Vink, {G. R.} and M. Koopman and {van Iersel}, Liselot and {PLCRC-MEDOCC group}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = aug,

day = "20",

doi = "10.1186/s12885-020-07252-y",

language = "English",

volume = "20",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central Ltd",

number = "1",

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Schraa, SJ, van Rooijen, KL, van der Kruijssen, DEW, Alarcon, CR, Phallen, J, Sausen, M, Simmons, J, Coupe, VMH, van Grevenstein, WMU, Elias, S, Verkooijen, HM, Lacle, MM, Bosch, LJW, van den Broek, D, Meijer, GA, Velculescu, VE, Fijneman, RJA, Vink, GR, Koopman, M , van Iersel, L & PLCRC-MEDOCC group 2020, 'Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study', BMC Cancer, vol. 20, no. 1, 790. https://doi.org/10.1186/s12885-020-07252-y

TY - JOUR

T1 - Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE)

T2 - study protocol for a trial within a cohort study

AU - Schraa, S. J.

AU - van Rooijen, K. L.

AU - van der Kruijssen, D. E. W.

AU - Alarcon, C. Rubio

AU - Phallen, J.

AU - Sausen, M.

AU - Simmons, J.

AU - Coupe, V. M. H.

AU - van Grevenstein, W. M. U.

AU - Elias, S.

AU - Verkooijen, H. M.

AU - Lacle, M. M.

AU - Bosch, L. J. W.

AU - van den Broek, D.

AU - Meijer, G. A.

AU - Velculescu, V. E.

AU - Fijneman, R. J. A.

AU - Vink, G. R.

AU - Koopman, M.

AU - van Iersel, Liselot

AU - PLCRC-MEDOCC group

PY - 2020/8/20

Y1 - 2020/8/20

N2 - BackgroundAccurate 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/designMEDOCC-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 (TM) platform. Patients with detectable ctDNA will be offered ACT consisting of 8cycles 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.DiscussionThe 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 registrationNetherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281

AB - BackgroundAccurate 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/designMEDOCC-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 (TM) platform. Patients with detectable ctDNA will be offered ACT consisting of 8cycles 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.DiscussionThe 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 registrationNetherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281

KW - Colon cancer

KW - Circulating tumor DNA

KW - ctDNA

KW - Adjuvant chemotherapy

KW - TwiCs

KW - RANDOMIZED CONTROLLED-TRIAL

KW - CELL-FREE DNA

KW - COLORECTAL-CANCER

KW - RESIDUAL DISEASE

KW - FLUOROURACIL

KW - RECURRENCE

KW - SURVIVAL

KW - LEUCOVORIN

KW - RISK

KW - OXALIPLATIN

U2 - 10.1186/s12885-020-07252-y

DO - 10.1186/s12885-020-07252-y

M3 - Article

C2 - 32819390

SN - 1471-2407

VL - 20

JO - BMC Cancer

JF - BMC Cancer

IS - 1

M1 - 790

ER -