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

Colon Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04259944
• Other study ID #: IFOM-CPT005/2019/PO004
• Secondary ID: 2019-002074-32
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 16, 2020
• Est. completion date: October 15, 2024

Study information

• Verified date: September 2023
• Source: IFOM ETS - The AIRC Institute of Molecular Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. completion date: October 15, 2024
• Est. primary completion date: July 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:- Patients having a MSI-H/MMRd tumor are excluded from the study (done according to standard clinical practice).

• 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).

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Italy	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	Padova
Italy	Ospedale Santa Maria della Misericordia	Perugia
Italy	AULS della Romagna	Ravenna
Spain	University Hospital del Mar	Barcelona
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Moises Broggi	Sant Joan Despí	Barcelona
Spain	INCLIVA Biomedical Research Institute	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
IFOM ETS - The AIRC Institute of Molecular Oncology	Guardant Health, Inc.

Countries where clinical trial is conducted

Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease-Free Survival (DFS)		2 & 3 years
Secondary	Overall Survival (OS)		5 years
Secondary	Safety and tolerability according to CTCAE version 5.0		2 years
Secondary	Assessment of QLQ-C30 and CR-29 EORTC questionnaires		2 years
Secondary	Number of patients experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any chemotherapy regimen remaining disease free		2 & 3 years