PEGASUS is a prospective multi-centric study designed to prove the feasibility of using liquid biopsy to guide the post-surgical and post-adjuvant clinical management in 140 microsatellite stable Stage-III and T4N0 Stage-II colon cancer patients.
The LUNAR1 Test (Guardant Health, Redwood City, CA, USA) will be used for ctDNA determination. For the efficacy analysis, the PEGASUS cohort will be compared with a cohort of 420 patients from the TOSCA trial (NCT00646607) population matched 3:1 for all known prognostic phenotypes. A post-surgical LB executed 2-4 weeks after surgery will guide a "Molecular Adjuvant" treatment as follows: i) ctDNA+ patients will receive CAPOX for 3 months; ii) ctDNA- patients will receive capecitabine (CAPE) for 6 months but will be retested after 1 cycle, and if found ctDNA+ will be switched to CAPOX treatment. Immediately after the end of the "Molecular Adjuvant" treatment a further LB will be performed and instruct subsequent treatment. Positive patients (ctDNA+/+ and ctDNA-/+) will receive an up-scaled "Molecular Metastatic" systemic treatment for 6 months or until radiological progression or toxicity as follows: i) ctDNA+/+ patients will be treated with FOLFIRI; ii) ctDNA-/+ patients with CAPOX. These patients will be subjected to a LB after 3 months at the end of treatment and in case of positivity will be switched to FOLFIRI. Patients experiencing ctDNA conversion to negative (ctDNA+/-) will receive a de-escalated treatment with CAPE for 3 months. 3 LB will be performed within 3 months and in case of positivity the patient will be switched to FOLFIRI. Patients with ctDNA-/- will be subjected to an interventional follow-up comprising 2 further LB and in case of positivity they will be switched to CAPOX treatment. PEGASUS is piggybacked to AlfaOmega (NCT04120935), a Master Observational Protocol that will follow patients from diagnosis to 5 years or recurrence/death (whichever comes first), collecting clinical data, radio-images and biological samples. AlfaOmega provides a clinical and logistic ecosystem for the seamless integration of PEGASUS clinical results with the biological underpinning of colon cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
140
DAY 1 * OXA 130 mg/m2 administered as intravenous infusion over 2 hours in 250 mL dextrose 5% * CAPE 1000 mg/m2 administrated per os twice daily DAY 2-14 • CAPE 1000 mg/m2 os twice daily Cycle length is 3 weeks comprising 2 hours of oxaliplatin infusion every 21 days, 14 days of oral capecitabine and 7 days of resting.
DAY 1-14 • CAPE 1250 mg/m2 os twice daily Cycle length is 3 weeks comprising 14 days of oral capecitabine and 7 days of resting.
Day 1: * IRI, 180 mg/m2 administered as iv infusion over 30-90 minutes in 250 mL dextrose 5%, concurrently (via a Y-connector) with * LV, 400 mg/m2 administered as an iv infusion over 2 hours, in 250 mL dextrose 5%, followed by * 5-FU, 400 mg/m2 administered as a bolus injection (iv push administered by hand) and then at 2400 mg/m2 administered as a iv infusion over 46 hours. Cycle length is 2 weeks comprising approximately 48 hours of infusion and 12 days of rest.
Ospedale Policlinico San Martino IRCCS
Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Europeo di Oncologia IRCCS
Milan, Italy
Number of post-surgery and post-adjuvant false negative cases after a double ctDNA-negative detection
Cases that become positive at subsequent interventional LB or that experience radiological relapse
Time frame: 2 years
Disease-Free Survival (DFS)
Time frame: 2 & 3 years
Overall Survival (OS)
Time frame: 5 years
Safety and tolerability according to CTCAE version 5.0
Time frame: 2 years
Assessment of QLQ-C30 and CR-29 EORTC questionnaires
Time frame: 2 years
Number of patients experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any chemotherapy regimen remaining disease free
Time frame: 2 & 3 years
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Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
Istituto Oncologico Veneto IRCCS
Padova, Italy
Ospedale Santa Maria della Misericordia
Perugia, Italy
AULS della Romagna
Ravenna, Italy
Hospital Moises Broggi
Sant Joan Despí, Barcelona, Spain
University Hospital del Mar
Barcelona, Spain
Vall d'Hebron Institute of Oncology
Barcelona, Spain
...and 1 more locations