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NCT Number: 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

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.

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Key information

Conditions

Rectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS

Aviano, Pordenone, 33081, Italy

Location contact

Elena De Mattia, PhD

SUB_INVESTIGATOR

Elisa Palazzari, MD

SUB_INVESTIGATOR

Erika Cecchin, PhD

CONTACT

[email protected]

0434 659 667

Erika Cecchin, PhD

PRINCIPAL_INVESTIGATOR

Federico Navarria, MD

SUB_INVESTIGATOR

Giuseppe Toffoli, MD

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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

    Relation between rare and very rare genetic variants and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval

Secondary outcomes

  1. Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics

    Time frame: up to 5 years

    Mean difference between subgroup of patients with different genetics characteristics

  2. Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response

    Time frame: up to 5 years

    Relation between plasma levels of IL-17F and SMAD3 proteins and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval

  3. Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour.

    Time frame: up to 5 years

    Relation between plasma levels of IL-17F and SMAD3 and disease-free survival (DFS) defined as time between enrollment and objective tumor progression using Kaplan Meyer method

  4. Identify further genetic markers of pathological tumour response

    Time frame: up to 5 years

    Relation between selected genetic markers and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval

  5. Define the role of the same genetic polymorphisms on disease-free survival

    Time frame: up to 5 years

    Relation between selected genetic markers and disease-free survival (DFS) defined as time between enrollment and objective tumor progression using Kaplan Meyer method

  6. Define the role of the same genetic polymorphisms on overall survival of patients

    Time frame: up to 5 years

    Relation between selected genetic markers and overall survival (OS) defined as time between enrollment and death from any cause using Kaplan Meyer method

  7. Define the role of the same genetic polymorphisms on the risk of developing severe treatment toxicities

    Time frame: up to 5 years

    Relation between genetic variants and severe treatment toxicity will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval

Study contacts

Contact information is provided by the study sponsor or research team.

Erika Cecchin, PhD

CONTACT

[email protected]

0434 659 667

Sponsors and collaborators

Lead sponsor

Centro di Riferimento Oncologico - Aviano

Other

Registry information

Acronym: IGLarc

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Sep 27, 2024
Registry last updated
Sep 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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