Stage II/III Colorectal Cancer Recurrence

Официальное название

Predicting Recurrence-Free Survival in Stage III and High-Risk Stage II Colorectal Cancer After Curative-Intent Treatment

Обзор

This study will develop an assay to predict disease recurrence in patients with stage II/III CRC after receiving adjuvant chemotherapy, using genome-wide DNA methylation.

Подробное описание

Adjuvant chemotherapy (ACT) is the standard clinical care for patients with stage III or high-risk stage II colorectal cancer (CRC) after curative-intent resection. Nonetheless, more than 30% of patients experience CRC recurrence. Accurate prediction of recurrence risk in stage II/III CRC patients who undergo ACT is crucial for determining the necessity and duration of ACT, as well as for tailoring novel treatment strategies for these patients.

This study will comprise three phases

1. A systematic and comprehensive CpG methylation-based epigenetic biomarker discovery phase to identify the differentially methylated CpG sites associated with recurrence-free survival (RFS) \< 5 years and \> 5 years. In this phase, LASSO-based machine learning algorithms will be used to optimize the biomarker candidates. 2. A tissue-based clinical assay development phase by quantitative pyrosequencing 3. An independent validation phase.

At completion, this study will validate a tissue-based assay to predict the development of recurrence after the completion of chemotherapy in patients with stage III and II CRC

Вмешательства

• Другое CENSURE
  A panel of CpG sites, whose methylation level is tested in macro-dissected formalin-fixed and paraffin-embedded (FFPE) samples derived from the primary tumor.

Первичные конечные точки

• Recurrence-Free Survival [Срок оценки: Up to 120 months]

Вторичные конечные точки (1)

• Overall Survival [Срок оценки: Up to 120 months]

Критерии участия

Критерии включения

• Stage II (high-risk) or III colorectal cancer (TNM classification, 8th edition).
• Received standard diagnostic, staging, and therapeutic procedures as per local guidelines
• Received stage-specific curative-intent resection followed by adjuvant chemotherapy.
• Confirmed cancer-free survivorship confirmed at the time of study inclusion.

Критерии исключения

• Lack of written informed consent.
• Development of recurrence in the first 6 months following adjuvant chemotherapy completion.
• Hereditary colorectal cancer syndromes (identified through genetic testing)
• Inflammatory bowel diseases

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Испания · 2 центра

• Barcelona University — Barcelona
• La Paz University Hospital — Madrid

США · 1 центр

• City of Hope Medical Center — Monrovia

Китай · 1 центр

• Second Affiliated Hospital of Dalian Medical University — Dalian

Публикации

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. PMID 36633525
• Frei AL, McGuigan A, Sinha RRAK, Jabbar F, Gneo L, Tomasevic T, Harkin A, Iveson T, Saunders MP, Oien KA, Maka N, Pezzella F, Campo L, Browne M, Glaire M, Kildal W, Danielsen HE, Hay J, Edwards J, Sansom O, Kelly C, Tomlinson I, Kerr R, Kerr D, Domingo E; TransSCOT consortium; Church DN, Koelzer VH. Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II-III c PMID 38301689
• Argiles G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T, Laurent-Puig P, Quirke P, Yoshino T, Taieb J, Martinelli E, Arnold D; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Oct;31(10):1291-1305. doi: 10.1016/j.annonc.2020.06.022. Epub 2020 Ju PMID 32702383
• Liu Z, Guo C, Dang Q, Wang L, Liu L, Weng S, Xu H, Lu T, Sun Z, Han X. Integrative analysis from multi-center studies identities a consensus machine learning-derived lncRNA signature for stage II/III colorectal cancer. EBioMedicine. 2022 Jan;75:103750. doi: 10.1016/j.ebiom.2021.103750. Epub 2021 Dec 15. PMID 34922323
• Feng Q, Chang W, Mao Y, He G, Zheng P, Tang W, Wei Y, Ren L, Zhu D, Ji M, Tu Y, Qin X, Xu J. Tumor-associated Macrophages as Prognostic and Predictive Biomarkers for Postoperative Adjuvant Chemotherapy in Patients with Stage II Colon Cancer. Clin Cancer Res. 2019 Jul 1;25(13):3896-3907. doi: 10.1158/1078-0432.CCR-18-2076. Epub 2019 Apr 15. PMID 30988081
• Osterman E, Glimelius B. Recurrence Risk After Up-to-Date Colon Cancer Staging, Surgery, and Pathology: Analysis of the Entire Swedish Population. Dis Colon Rectum. 2018 Sep;61(9):1016-1025. doi: 10.1097/DCR.0000000000001158. PMID 30086050
• Varghese A. Chemotherapy for Stage II Colon Cancer. Clin Colon Rectal Surg. 2015 Dec;28(4):256-61. doi: 10.1055/s-0035-1564430. PMID 26648796

Идентификаторы

NCT: NCT06314958 · 23228/CENSURE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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