Study of the Predictive and Prognostic Role of Pharmacogenetic and Radiogenic Variants on the Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

Обзор

In locally advanced rectal cancer the pathological complete response (pCR) to neoadjuvant chemoradiation therapy (nCRT) is associated with a favourable long-term prognosis. The identification of markers predictive of response to therapy would therefore optimise treatment by allowing personalised therapy. It has been shown that the genetic profile of the patient could influence the activation of the immune system in combination with chemoradiation therapy in targeting tumour cells. In addition, genetic features of molecular pathways correlated with response to chemoradiotherapy, may in turn affect the probability of a good response to treatment in these patients, but also the occurrence of adverse events. The main objective of the study is to define the role of genetic markers related to immune system activation and other molecular pathways in predicting the complete pathological response to preoperative chemoradiation therapy in patients with locally advanced rectal cancer.

Первичные конечные точки

• Defining the predictive role of rare (MAF<1%) and very rare genetic variants (MAF<0.1%) in the SMAD3 and IL-17F genes, implicated in nCRT-mediated activation of the immune system on the pathological tumour response to nCRT in LARC. [Срок оценки: up to 5 years]

Вторичные конечные точки (7)

• Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics [Срок оценки: up to 5 years]
• Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response [Срок оценки: up to 5 years]
• Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour. [Срок оценки: up to 5 years]
• Identify further genetic markers of pathological tumour response [Срок оценки: up to 5 years]
• Define the role of the same genetic polymorphisms on disease-free survival [Срок оценки: up to 5 years]
• Define the role of the same genetic polymorphisms on overall survival of patients [Срок оценки: up to 5 years]
• Define the role of the same genetic polymorphisms on the risk of developing severe treatment toxicities [Срок оценки: up to 5 years]

Критерии участия

Eligibility criteria:

• histologically confirmed diagnosis of primary resectable LARC;
• confirmed absence of distant metastases;
• ≥18 years old;
• stage of disease T3-T4 and N0-N2;
• performance status (World Health Organisation) 0-2;
• normal bone marrow, kidney and liver function;

Критерии исключения

• evidence of secondary tumour
• inadequate liver function (bilirubin >1.5 times the normal range, ALT and AST >2 times the normal range);
• inadequate renal function (creatinine >1.5 times the upper limit of normal range);
• Major concomitant systemic diseases that contraindicate surgery;
• significant cardiovascular disease (heart failure, acute myocardial infarction within the last year, active angina, cardiac arrhythmia to be treated, uncontrolled hypertension)
• systemic disease contraindicating radiotherapy

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS — Aviano

Идентификаторы

NCT: NCT06616870 · CRO-2023-77

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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