A personalised approach based on blood and tumor characteristics to guide the post-surgical clinical path of patients with operable locoregional colon cancer

Phase 1

• Conditions: Colon cancer; MedDRA version: 21.0Level: PTClassification code: 10010034Term: Colorectal cancer stage III Class: 100000004864; MedDRA version: 21.0Level: PTClassification code: 10010033Term: Colorectal cancer stage II Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-509851-15-00
• Lead Sponsor: Ifom Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-09
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

SAGITTARIUS trial written informed consent., Age = 18 years., Histologically confirmed diagnosis of operable stage III and High-Risk stage II colon cancer located at least 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery., Availability of the original FFPE tumor tissue., ECOG performance status 0-1., Normal organ functions (as defined in section 8.3 of the Protocol)., Women with childbearing potential (WOCBP) should complete a pregnancy test and be willing to use highly effective contraceptive methods.

Exclusion Criteria

History of another neoplastic disease, unless in remission for = 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded., Has a known DPD (DihydroPyrimidine Dehydrogenase) deficiency., Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant., Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required., Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection, Has a known history of active TB (Bacillus Tuberculosis)., Had an incomplete diagnostic colonoscopy., Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage)., Recent polyps’ removal (within one month)., Current or recent treatment with another investigational drug or participation in another investigational study., Patient unable to comply with the study protocol owing to psychological, social or geographical reasons., Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study., Inadequate contraception (male or female patients) if of childbearing or procreational potential., Clinically relevant cardiovascular disease., Acute or subacute intestinal occlusion or history of inflammatory bowel disease or any other autoimmune disease., Has a medical condition that contraindicate the use of the investigational medicinal product (IMP) according to product indications., Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To prove that a personalized ctDNA-guided genomic-based targeted treatment strategy can improve the clinical outcome of Stage III and High-Risk Stage II CC patients as respect to a conventional adjuvant chemotherapy approach.;Secondary Objective: To compare the 2-year RFS of the prior declared physician choice chemotherapy versus downsized treatment in ctDNA-negative patients (Trial-2)., To compare the toxicity and quality of life of personalized versus conventional adjuvant strategies (Trial-1 and Trial-2)., To compare the economic toxicity of personalized versus conventional adjuvant strategies., To establish the false negative rate of serial LBs in the experimental arms of Trial-1 and Trial-2.;Primary end point(s): 2-year RFS in patients with a post-surgery ctDNA positivity randomized 1:1 to receive either a conventional adjuvant chemotherapy or a personalized targeted treatment strategy.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):2-year RFS in patients with a post-surgery ctDNA negativity randomized 1:1 to receive either a physician-choice adjuvant therapy or an intensive follow-up strategy.;Secondary end point(s):3 and 5-year RFS and OS in patients with a post-surgery ctDNA positivity (Trial-1) and ctDNA negativity (Trial-2) randomized either in the conventional or experimental Trials.;Secondary end point(s):Safety and tolerability according to Clinical Trials Criteria for Adverse Events (CTCAE) version 5.0 (Trial-1, Trial-2 and whole study population).;Secondary end point(s):Number of false negative cases after three consecutive negative LBs, defined as cases that experience radiological relapse within 2 years.;Secondary end point(s):Number of patients experiencing ctDNA seroconversion (i.e., ctDNA+ that become ctDNA-) after any therapy regimen remaining disease free at 2 and 3 years;Secondary end point(s):Assessment of FACT-C and EQ-5D-5L questionnaires in the whole study population.