Dynamic Changes in Circulating Tumour Cells Protein Expression (Liquid-DRER2)

Dynamic Changes in RAS Gene Status and HER2 Expression in Circulating Tumour Cells: a Phase II Trial

This multicenter study, randomized, controlled of blood-based biomarker-driven targhet therapy. Patients were selectedm( at Hospital San Giovanni and Celio in Rome) according to CTCs results ( CTCs-guided managment performed at University Magna Graecia) or managed by the treating clinician according to standard pathological criteria (standard management). The participants were assigned to trial groups with the use of block randomization stratified according to the enrolling center location metropolitan) and tumor stage (T3 or T4).

Study Overview

• Status: Recruiting
• Conditions: Recurrence Free Survival
• Intervention / Treatment: Drug: panitumumab (EGFR inhibitors)

Detailed Description

The investigators enroll patients with histologically confirmed advanced stage (T3 or T4, N1/2, M0/1) colorectal adenocarcinoma with molecular analysis on RAS mutant status. The participants are enrolled within 3 weeks at the time of progression disease (PD) from any line of therapy. Blood samples were collected from each participant after obtaining informed consent. Permission to perform CTCs analysis from blood was obtained from the Regional Ethical Committee (No.2013/34) and the study is conducted in accordance with the Declaration of Helsinki.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Natalia Malara, prof; Phone Number: 03489705145; Email: nataliamalara@unicz.it
• Study Contact Backup: Name: Natalia Malara; Email: nataliamalara@unicz.it

Study Locations

• Italy
  • Italy
    • Germaneto, Italy, Italy, 88100
      • Recruiting
      • Natalia Malara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 to 2 (scores range from 0 to 5, with higher numbers reflecting greater disability) ,
• medically able to receive chemotherapy.

Exclusion Criteria:

• evidence of infective disease before enrollment ,
• a history of another primary cancer within the previous 3 years,
• the presence of synchronous primary colorectal cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAS unmutated CTCs HER positive	Drug: panitumumab (EGFR inhibitors); Chemotherapy treatment includes anti-EGFR biologics such as cetuximab or panitumumab, antiangiogenic drugs such as bevacizumab or aflibercept. The indication to treat depends from the presence of CTCs analysed for Ras mutation and HER2 expression
Experimental: CTCs	Drug: panitumumab (EGFR inhibitors); Chemotherapy treatment includes anti-EGFR biologics such as cetuximab or panitumumab, antiangiogenic drugs such as bevacizumab or aflibercept. The indication to treat depends from the presence of CTCs analysed for Ras mutation and HER2 expression
Experimental: RAS unmutated CTCs HER negative	Drug: panitumumab (EGFR inhibitors); Chemotherapy treatment includes anti-EGFR biologics such as cetuximab or panitumumab, antiangiogenic drugs such as bevacizumab or aflibercept. The indication to treat depends from the presence of CTCs analysed for Ras mutation and HER2 expression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy end point was Objective Responsive Rate (ORR) at 12 months.	12 months

Collaborators and Investigators

• Sponsor: Matteo's Friends

Publications and helpful links

General Publications

• Malara N, Donato G, Ferrazzo F, Garo NC, Fulciniti F. The Charactex Protocol for Blood-Derived Cytological Preparation of Nonhematological Cancer. Acta Cytol. 2023;67(3):295-303. doi: 10.1159/000527904. Epub 2022 Dec 12.
• Malara N, Coluccio ML, Grillo F, Ferrazzo T, Garo NC, Donato G, Lavecchia A, Fulciniti F, Sapino A, Cascardi E, Pellegrini A, Foxi P, Furlanello C, Negri G, Fadda G, Capitanio A, Pullano S, Garo VM, Ferrazzo F, Lowe A, Torsello A, Candeloro P, Gentile F. Multicancer screening test based on the detection of circulating non haematological proliferating atypical cells. Mol Cancer. 2024 Feb 13;23(1):32. doi: 10.1186/s12943-024-01951-x.
• Malara N, Trunzo V, Foresta U, Amodio N, De Vitis S, Roveda L, Fava M, Coluccio M, Macri R, Di Vito A, Costa N, Mignogna C, Britti D, Palma E, Mollace V. Ex-vivo characterization of circulating colon cancer cells distinguished in stem and differentiated subset provides useful biomarker for personalized metastatic risk assessment. J Transl Med. 2016 May 12;14(1):133. doi: 10.1186/s12967-016-0876-y.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Actual): December 17, 2024
• Study Completion (Estimated): December 18, 2027

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplastic Processes; Neoplasm Metastasis; Recurrence; Neoplastic Cells, Circulating; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Panitumumab
• Other Study ID Numbers: 2013.34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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