Prediction of True Oligo-metastatic Disease. (PREDICTION)

Oligo-metastatic neoPlasms From the gastRo-intEstinal Tract: iDentIfiCaTIon Of cliNical and Molecular Drivers: the PREDICTION Study

In recent years, the scientific community has recognized the need to differentiate between poly- and oligo-metastatic disease (OMD) in oncology due to their distinct clinical and biological behavior. The definition of "true" and good-prognosis OMD is necessarily retrospective, as many patients initially considered oligo-metastatic develop poly-metastatic disease within one year. The PREDICTION study is a prospective, observational, and monocentric investigation. The study has two primary objectives. The first one is descriptive and aims to determine the prevalence of specific biological characteristics in OMD derived from gastrointestinal tract neoplasms (colon, stomach, biliary tract, exocrine glands of the digestive tract). These biological characteristics include genetic landscape and T lymphocyte infiltrate of the primary tumor and/or metastases. Genetic assessment will be done on formalin-fixed paraffin-embedded (FFPE) tissues or liquid biopsies with the Oncomine Solid Tumour DNA kit (Thermo Fisher Scientific, Waltham, MA, USA). Data analysis will be performed using the Torrent Suite Software v5.0 (Thermo Fisher Scientific). The analysis of T lymphocytes will be conducted through immunohistochemistry (IHC) in primary and or metastatic tissues (if available). The second co-primary objective aims to identify OMD through the prognostic effect of a score designed ad hoc. It is tested in a single pathology, namely in patients with metastatic colorectal cancer. A score is constructed based on the following characteristics, with possession of all characteristics (3+) constituting the full score: a primitive/metastasis genetic concordance >80% = 1 point; high T-lymphocyte infiltration GRZB+ (>10 cells/mm2) in the primary tumor and/or metastases (where tissue is available) = 1 point; absence of clonal evolution favoring specific key-driver genes = 1 point. The hypothesis is that patients with true OMD (score 3+) have a significantly lower rate of progression at one year, defined as recurrence after radical surgery or progression (in oligometastatic patients who are not candidates for upfront definitive local treatment) based on RECIST v 1.1 criteria since enrollment in the study, compared to those with false OMD who subsequently develop polymetastatic disease. The treatments will be chosen at the discretion of the referring Oncologist, in multidisciplinary sessions, according to normal clinical practice. The sample size was determined using a two-sided test of difference between proportions to evaluate the statistical significance of the difference in recurrence within 1 year. For this purpose, the following scenario was considered: a reasonable probability of the simultaneous occurrence of the 3 factors in true OMD (score 3+) of 60%; a recurrence rate of 20% for true OMD (score 3+), and 80% for false OMD (score <3+). With a significance level of α=0.05, a test power of 90%, and a Fisher exact test, the required number of patients to be enrolled is 32, to be recruited over an expected period of 2 years.

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Disease
• Intervention / Treatment: Diagnostic test: Genetic and immunologic assessments

• Study Type: Observational
• Enrollment (Anticipated): 32

Contacts and Locations

• Study Contact: Name: Alessandro Ottaiano; Phone Number: +39 081 17770344; Email: a.ottaiano@istitutotumori.na.it
• Study Contact Backup: Name: Mariachiara Santorsola; Phone Number: +39 081 17770344; Email: mariachiara.santorsola@istitutotumori.na.it

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Alessandro Ottaiano
    • Contact: Alessandro Ottaiano, MD; Phone Number: 0815903510; Email: a.ottaiano@istitutotumori.na.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients affected by gastroenteric tumors (colon, stomach, biliary tract, exocrine glands of the digestive tract) with oligo-metastatic disease. Oligometastatic patients will be defined as those presenting with one to three lesions per organ with a maximum tumor diameter of less than 70 mm and no lesion with a diameter greater than 25 mm.

Description

Inclusion Criteria:

• Patients eligible for inclusion in this study must meet the following criteria:
• Diagnosis of gastroenteric tumors (colon, stomach, biliary tract, exocrine glands of the digestive tract);
• OMD: one to three lesions per organ with a maximum tumor diameter of less than 70 mm and no lesion with a diameter greater than 25 mm;
• Availability of FFPE (Formalin Fixed Paraffin Embedded) inclusions from resected primary tumor;
• Written informed consent.

Exclusion Criteria:

• Previous or concurrent malignant neoplasms;
• Presence of cerebral metastases;
• Refusal or inability to provide informed consent;
• Inability to guarantee follow-up.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression/Recurrence	Rate of recurrence/progression within one year	1 year

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer
• Other Study ID Numbers: NCINaples

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No