Post-surgical Liquid Biopsy-guided Treatment of Stage III and High-risk Stage II Colon Cancer Patients: the PEGASUS Trial
2 other identifiers
interventional
140
2 countries
11
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2020
Typical duration for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 5, 2020
CompletedFirst Posted
Study publicly available on registry
February 7, 2020
CompletedStudy Start
First participant enrolled
June 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 15, 2024
CompletedSeptember 28, 2023
September 1, 2023
4.1 years
February 5, 2020
September 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
2 years
Secondary Outcomes (5)
Disease-Free Survival (DFS)
2 & 3 years
Overall Survival (OS)
5 years
Safety and tolerability according to CTCAE version 5.0
2 years
Assessment of QLQ-C30 and CR-29 EORTC questionnaires
2 years
Number of patients experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any chemotherapy regimen remaining disease free
2 & 3 years
Study Arms (1)
Liquid Biopsy-Guided Adjuvant Treatment
EXPERIMENTALA post-surgical LB executed 2-4 weeks after surgery will guide a "Molecular Adjuvant" treatment: * ctDNA+ patients: CAPOX for 3 months * ctDNA- patients: capecitabine (CAPE) for 6 months. LB after 1 cycle and if found ctDNA+ will be switched to CAPOX. A post-Molecular Adjuvant treatment LB will be performed and instruct subsequent treatment: * ctDNA+/+ patients: up-scale to a "Molecular Metastatic" treatment with FOLFIRI for 6 months or until radiological progression or toxicity; * ctDNA-/+ patients: up-scale to a "Molecular Metastatic" treatment with CAPOX for 6 months or until radiological progression or toxicity. LB after 3 months at the end of treatment and in case of positivity switch to FOLFIRI. * ctDNA+/- patients: de-escalate treatment to CAPE for 3 months. 3 LB performed within 3 months and in case of positivity switch to FOLFIRI. * ctDNA-/- patients: interventional follow-up comprising 2 further LB and in case of positivity switch to CAPOX treatment.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Pegasus trial written informed consent.
- Age ≥ 18 years.
- Histologically confirmed diagnosis of operable stage III or T4N0 stage II colon cancer located 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery.
- Availability of plasma collected prior to surgery.
- Availability of the original FFPE tumor tissue.
- Acceptance to undergo at least all the interventional liquid biopsies.
- ECOG performance status 0-1.
- Normal organ functions. (as defined in section 9.3)
- Women with childbearing potential should complete a pregnancy test and be willing to use highly effective contraceptive methods.
You may not qualify if:
- 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.
- Had an incomplete diagnostic colonoscopy and/or polyps removal.
- 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).
- 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.
- Pre-existing neuropathy \> grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
- 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. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a known history of active TB (Bacillus Tuberculosis).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Ospedale Policlinico San Martino IRCCS
Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Europeo di Oncologia IRCCS
Milan, Italy
Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
Istituto Oncologico Veneto IRCCS
Padua, Italy
Ospedale Santa Maria della Misericordia
Perugia, 06132, Italy
AULS della Romagna
Ravenna, 48121, Italy
Hospital Moises Broggi
Sant Joan Despí, Barcelona, 08970, Spain
University Hospital del Mar
Barcelona, Spain
Vall d'Hebron Institute of Oncology
Barcelona, Spain
INCLIVA Biomedical Research Institute
Valencia, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Sara Lonardi, MD
Istituto Oncologico Veneto IRCCS
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2020
First Posted
February 7, 2020
Study Start
June 16, 2020
Primary Completion
July 15, 2024
Study Completion
October 15, 2024
Last Updated
September 28, 2023
Record last verified: 2023-09