NCT04259944

Post-surgical Liquid Biopsy-guided Treatment of Stage III and High-risk Stage II Colon Cancer Patients: the PEGASUS Trial

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Colon Cancer

Interventions

Type	Name	Description
DRUG	CAPOX	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.
DRUG	Capecitabine	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.
DRUG	FOLFIRI	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.

Timeline

• Start date: 2020-06-16
• Primary completion: 2024-07-15
• Completion: 2024-10-15
• First posted: 2020-02-07
• Last updated: 2023-09-28

Locations

11 sites across 2 countries: Italy, Spain