Clinical trial NCT06616870: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Rectal Cancer
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2024-09-27
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a histologically confirmed diagnosis of primary resectable LARC

Brief summary: 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.


Eligibility criteria: Eligibility criteria:

1. histologically confirmed diagnosis of primary resectable LARC;
2. confirmed absence of distant metastases;
3. ≥18 years old;
4. stage of disease T3-T4 and N0-N2;
5. performance status (World Health Organisation) 0-2;
6. normal bone marrow, kidney and liver function;

Exclusion Criteria:

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

Primary outcomes:
measure: 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.
timeFrame: up to 5 years
Secondary outcomes:
measure: Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics
timeFrame: up to 5 years
measure: Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response
timeFrame: up to 5 years
measure: Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour.
timeFrame: up to 5 years
measure: Identify further genetic markers of pathological tumour response
timeFrame: up to 5 years
measure: Define the role of the same genetic polymorphisms on disease-free survival
timeFrame: up to 5 years
measure: Define the role of the same genetic polymorphisms on overall survival of patients
timeFrame: up to 5 years
measure: Define the role of the same genetic polymorphisms on the risk of developing severe treatment toxicities
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
state: Pordenone
Study officials:
affiliation: Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
name: Erika Cecchin, PhD
role: PRINCIPAL_INVESTIGATOR
References: