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

NCT06616870 | Not Yet Recruiting

• 1 other identifier: CRO-2023-77
• Study Type: observational
• Target: 460
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Outcome Measures

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.

  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

  up to 5 years

Secondary Outcomes (7)

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

  up to 5 years

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

  up to 5 years

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

  up to 5 years

• Identify further genetic markers of pathological tumour response

  up to 5 years

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

  up to 5 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a histologically confirmed diagnosis of primary resectable LARC

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro di Riferimento Oncologico - Aviano: lead

Study Sites (1)

Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS

Aviano, Pordenone, 33081, Italy

Location

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Erika Cecchin, PhD

  Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erika Cecchin, PhD

CONTACT

0434 659 667; ececchin@cro.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: September 27, 2024
• Study Start: October 3, 2024
• Primary Completion (Estimated): October 3, 2029
• Study Completion (Estimated): October 3, 2029
• Last Updated: September 27, 2024

Record last verified: 2024-09

Locations

IT (1)