ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C)
Abstract Background Circulating tumour DNA (ctDNA) to detect minimal residual disease (MRD) is emerging as a biomarker to predict recurrence in patients with curatively treated early stage colorectal cancer (CRC). ctDNA risk stratifies patients to guide adjuvant treatment decisions. We are conductin...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-10699-4 |
| _version_ | 1797864464801857536 |
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| author | Susanna Slater Annette Bryant Hsiang-Chi Chen Ruwaida Begum Isma Rana Maria Aresu Clare Peckitt Oleg Zhitkov Retchel Lazaro-Alcausi Victoria Borja Rachel Powell David Lowery Michael Hubank Thereasa Rich Gayathri Anandappa Ian Chau Naureen Starling David Cunningham |
| author_facet | Susanna Slater Annette Bryant Hsiang-Chi Chen Ruwaida Begum Isma Rana Maria Aresu Clare Peckitt Oleg Zhitkov Retchel Lazaro-Alcausi Victoria Borja Rachel Powell David Lowery Michael Hubank Thereasa Rich Gayathri Anandappa Ian Chau Naureen Starling David Cunningham |
| author_sort | Susanna Slater |
| collection | DOAJ |
| description | Abstract Background Circulating tumour DNA (ctDNA) to detect minimal residual disease (MRD) is emerging as a biomarker to predict recurrence in patients with curatively treated early stage colorectal cancer (CRC). ctDNA risk stratifies patients to guide adjuvant treatment decisions. We are conducting the UK’s first multi-centre, prospective, randomised study to determine whether a de-escalation strategy using ctDNA to guide adjuvant chemotherapy (ACT) decisions is non-inferior to standard of care (SOC) chemotherapy, as measured by 3-year disease free survival (DFS) in patients with resected CRC with no evidence of MRD (ctDNA negative post-operatively). In doing so we may be able to spare patients unnecessary chemotherapy and associated toxicity and achieve significant cost savings for the National Health Service (NHS). Methods We are recruiting patients with fully resected high risk stage II and stage III CRC who are being considered for ACT into the study which uses results from a plasma-only ctDNA assay to guide treatment decisions. Eligible patients are randomised 1:1 to receive ctDNA-guided chemotherapy versus SOC chemotherapy. The primary endpoint is the difference in DFS at 3 years between the trial arms. Secondary endpoints include the proportion of patients in the ctDNA-guided arm who are ctDNA negative post-operatively and receive de-escalated ACT compared to the standard arm, the difference in overall survival (OS), neurotoxicity and quality of life between the arms, and the cost-effectiveness of ctDNA-guided therapy compared to SOC treatment. We hypothesise that using a ctDNA-guided approach to ACT decisions is non-inferior to SOC. Target accrual is 1621 patients over 4 years, which will provide a power of 80% with an alpha of 0.1 to demonstrate non-inferiority with a margin of 1.25 in survival of the ctDNA-guided approach compared to SOC. We anticipate approximately 50 UK centres will participate. The study opened with the Guardant Reveal plasma-only ctDNA assay in August 2022. Discussion The trial will determine whether ctDNA guided ACT is non-inferior to SOC ACT in patients with fully resected high risk stage II and stage III resected CRC, with the potential to significantly reduce unnecessary ACT and the toxicity associated with it. Trial registration NCT04050345. |
| first_indexed | 2024-04-09T22:52:22Z |
| format | Article |
| id | doaj.art-fd82327f73c3444fa40eeb618feddeee |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:52:22Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-fd82327f73c3444fa40eeb618feddeee2023-03-22T11:35:03ZengBMCBMC Cancer1471-24072023-03-012311910.1186/s12885-023-10699-4ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C)Susanna Slater0Annette Bryant1Hsiang-Chi Chen2Ruwaida Begum3Isma Rana4Maria Aresu5Clare Peckitt6Oleg Zhitkov7Retchel Lazaro-Alcausi8Victoria Borja9Rachel Powell10David Lowery11Michael Hubank12Thereasa Rich13Gayathri Anandappa14Ian Chau15Naureen Starling16David Cunningham17Royal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustBiomedical Research Centre at the Royal Marsden and the Institute of Cancer ResearchCentre for Molecular Pathology at the The Royal Marsden Hospital and Institute of Cancer ResearchGuardant Health, INCRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustRoyal Marsden Hospital NHS Foundation TrustAbstract Background Circulating tumour DNA (ctDNA) to detect minimal residual disease (MRD) is emerging as a biomarker to predict recurrence in patients with curatively treated early stage colorectal cancer (CRC). ctDNA risk stratifies patients to guide adjuvant treatment decisions. We are conducting the UK’s first multi-centre, prospective, randomised study to determine whether a de-escalation strategy using ctDNA to guide adjuvant chemotherapy (ACT) decisions is non-inferior to standard of care (SOC) chemotherapy, as measured by 3-year disease free survival (DFS) in patients with resected CRC with no evidence of MRD (ctDNA negative post-operatively). In doing so we may be able to spare patients unnecessary chemotherapy and associated toxicity and achieve significant cost savings for the National Health Service (NHS). Methods We are recruiting patients with fully resected high risk stage II and stage III CRC who are being considered for ACT into the study which uses results from a plasma-only ctDNA assay to guide treatment decisions. Eligible patients are randomised 1:1 to receive ctDNA-guided chemotherapy versus SOC chemotherapy. The primary endpoint is the difference in DFS at 3 years between the trial arms. Secondary endpoints include the proportion of patients in the ctDNA-guided arm who are ctDNA negative post-operatively and receive de-escalated ACT compared to the standard arm, the difference in overall survival (OS), neurotoxicity and quality of life between the arms, and the cost-effectiveness of ctDNA-guided therapy compared to SOC treatment. We hypothesise that using a ctDNA-guided approach to ACT decisions is non-inferior to SOC. Target accrual is 1621 patients over 4 years, which will provide a power of 80% with an alpha of 0.1 to demonstrate non-inferiority with a margin of 1.25 in survival of the ctDNA-guided approach compared to SOC. We anticipate approximately 50 UK centres will participate. The study opened with the Guardant Reveal plasma-only ctDNA assay in August 2022. Discussion The trial will determine whether ctDNA guided ACT is non-inferior to SOC ACT in patients with fully resected high risk stage II and stage III resected CRC, with the potential to significantly reduce unnecessary ACT and the toxicity associated with it. Trial registration NCT04050345.https://doi.org/10.1186/s12885-023-10699-4Colorectal cancerctDNAAdjuvant chemotherapyRandomisedDisease free survival |
| spellingShingle | Susanna Slater Annette Bryant Hsiang-Chi Chen Ruwaida Begum Isma Rana Maria Aresu Clare Peckitt Oleg Zhitkov Retchel Lazaro-Alcausi Victoria Borja Rachel Powell David Lowery Michael Hubank Thereasa Rich Gayathri Anandappa Ian Chau Naureen Starling David Cunningham ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) BMC Cancer Colorectal cancer ctDNA Adjuvant chemotherapy Randomised Disease free survival |
| title | ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) |
| title_full | ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) |
| title_fullStr | ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) |
| title_full_unstemmed | ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) |
| title_short | ctDNA guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer: a multi-centre, prospective, randomised control trial (TRACC Part C) |
| title_sort | ctdna guided adjuvant chemotherapy versus standard of care adjuvant chemotherapy after curative surgery in patients with high risk stage ii or stage iii colorectal cancer a multi centre prospective randomised control trial tracc part c |
| topic | Colorectal cancer ctDNA Adjuvant chemotherapy Randomised Disease free survival |
| url | https://doi.org/10.1186/s12885-023-10699-4 |
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