Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer

Официальное название

Systemic Neoadjuvant and Adjuvant Control by Precision Medicine in Rectal Cancer (SYNCOPE) - Approach on High-risk Group to Reduce Metastases

Обзор

Rectal cancer represents the most complex area of multidisciplinary treatment in bowel surgery. In 2017, there were 1221 new rectal cancers in Finland. The prognosis of colorectal cancer (CRC) patients these days is almost exclusively driven by the occurrence of the metastatic form of the disease. The treatment of rectal cancer often includes a long delay between diagnosis and the initiation of systemic chemotherapy, increasing risk for systemic metastases for those at high risk. On the other hand, the waiting time during pretreatment before surgery enables comprehensive systematic characterization of the primary tumor status before the decisions on adjuvant chemotherapy, opening a window to the use of precision in decision-making. In this randomized controlled treatment trial, outcomes of novel precision methods to select right rectal cancer patients for treatment that they need will be compared to conventional treatment. The study aims to reduce over-treatment of those that most likely do not benefit from additional treatments. With the overall aim to reduce metastatic form of the disease, patients with high-risk features will be randomized to a treatment strategy with early systemic control by chemotherapy followed by circulating tumor DNA (ctDNA) and organoid-guided adjuvant therapy, or to conventional treatment strategy. Both state-of-the-art laboratory practice and routine diagnostic clinical pipelines are introduced to bring future diagnostic models of minimal residual disease and chemoresistance closer to current practice. The outcomes will reveal the clinical benefit of such strategy by recurrence-free survival at highest level of evidence, and produce important clinical outcome data on the application of ctDNA in everyday cancer treatment practice. The translational data on the use of ctDNA organoids to inform treatment decision and regimen selection will build knowledge of the use of such biomarkers as tools for clinical practice and clinical research. The results will be scalable worldwide in the practice of rectal cancer treatment.

Вмешательства

• Препарат Total neoadjuvant therapy (TNT)
  Short radiotherapy (5X5 Gy) and capecitabine/oxaliplatin
• Диагностический тест Minimal residual disease (MRD)
  Postoperative MRD on circulating cell-free DNA
• Лучевая терапия Long radiation therapy
  Long-course 50.4 Gy radiation with capecitabine

Первичные конечные точки

• Recurrence-free survival [Срок оценки: 3 years from surgery]
• Recurrence-free survival [Срок оценки: 5 years from surgery]
• Postoperative ctDNA [Срок оценки: 3 weeks postoperatively]

Вторичные конечные точки (12)

• CRC-specific survival [Срок оценки: 3 years]
• CRC-specific survival [Срок оценки: 5 years]
• overall survival [Срок оценки: 3 years]
• overall survival [Срок оценки: 5 years]
• number of surgically resected patients resected patients [Срок оценки: 1 year]
• R0-resection rate [Срок оценки: 1 year]
• local recurrence rate [Срок оценки: 5 years postoperatively]
• complete pathological response response rate [Срок оценки: 12 weeks after initiation of pretreatment]
• complete clinical response rate [Срок оценки: 12 weeks after initiation of pretreatment]
• total uptake of chemotherapy [Срок оценки: 1year]
• total uptake of chemotherapy [Срок оценки: 3 years]
• total uptake of chemotherapy [Срок оценки: 5 years]

Критерии участия

Критерии включения

• rectal adenocarcinoma,
• World Health Organization (WHO) performance status 0-1, assessed by the MDT to be able to undergo capecitabine and oxaliplatin (CAPOX) treatment, 3) extramural vein invasion by magnetic resonance imaging (mrEMVI+) and

4\) assessed by the multi-disciplinary team (MDT) to require either radiotherapy (RT) or long chemoradiotherapy (CRT) by the current standards.

Критерии исключения

• deficient mismatch repair (MMR) status,
• non-dihydropyrimidine dehydrogenase (DPYD) genotype,
• a contraindication to capecitabine, oxaliplatin or RT, or
• failing in blood tests that describe the adequate circulatory, liver and kidney function for chemotherapy.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Финляндия · 2 центра

• Helsinki University Central Hospital — Helsinki
• Tampere University Hospital — Tampere

Идентификаторы

NCT: NCT04842006 · HUS/155/2021

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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