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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Rectal Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Primary outcome measures
- 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. [Time frame: up to 5 years]
Secondary outcome measures (7)
- Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics [Time frame: up to 5 years]
- Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response [Time frame: up to 5 years]
- Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour. [Time frame: up to 5 years]
- Identify further genetic markers of pathological tumour response [Time frame: up to 5 years]
- Define the role of the same genetic polymorphisms on disease-free survival [Time frame: up to 5 years]
- Define the role of the same genetic polymorphisms on overall survival of patients [Time frame: up to 5 years]
- Define the role of the same genetic polymorphisms on the risk of developing severe treatment toxicities [Time frame: up to 5 years]
Eligibility criteria
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;
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Italy · 1 center
- Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS — Aviano
Identifiers
NCT: NCT06616870 · CRO-2023-77