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Colon CancerPhase 2NCT04259944

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

A Phase 2 study testing CAPOX, Capecitabine and FOLFIRI in people with Colon Cancer, run by IFOM ETS - The AIRC Institute of Molecular Oncology at 11 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer
What is being tested?
CAPOX, Capecitabine and FOLFIRI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
11 sitesin 2 countries
Study dates
16 Jun 2020to 15 Oct 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 25Show fewer
  • 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).

Who cannot join

None listed.

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

Italy7 sites

  • Ospedale Policlinico San Martino IRCCS

    Genova

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

  • Istituto Europeo di Oncologia IRCCS

    Milan

  • Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda

    Milan

  • Istituto Oncologico Veneto IRCCS

    Padova

  • Ospedale Santa Maria della Misericordia

    Perugia, 06132

  • AULS della Romagna

    Ravenna, 48121

Other trials in Italy

Spain4 sites

  • University Hospital del Mar

    Barcelona

  • Vall d'Hebron Institute of Oncology

    Barcelona

  • Hospital Moises Broggi

    Sant Joan Despí, Barcelona, 08970

  • INCLIVA Biomedical Research Institute

    Valencia

Other trials in Spain

About this study

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.

Read the 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
Being tested
CAPOX, Capecitabine, FOLFIRI
Keywords
liquid biopsy, colon cancer, adjuvant treatment, ctDNA, colorectal cancer, CAPOX, FOLFIRI, CAPE
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAPOXDrug

    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.

  • CapecitabineDrug

    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.

  • FOLFIRIDrug

    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.

Study groups in NCT04259944
Study groupRoleWhat they receive
Liquid Biopsy-Guided Adjuvant TreatmentExperimentalA 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.
Receives: Drug: CAPOX; Drug: Capecitabine; Drug: FOLFIRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 2 years

Secondary outcomes (5)

  1. Disease-Free Survival (DFS)

    Measured: 2 & 3 years

  2. Overall Survival (OS)

    Measured: 5 years

  3. Safety and tolerability according to CTCAE version 5.0

    Measured: 2 years

  4. Assessment of QLQ-C30 and CR-29 EORTC questionnaires

    Measured: 2 years

  5. Number of patients experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any chemotherapy regimen remaining disease free

    Measured: 2 & 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2020
  2. Study start16 Jun 2020
  3. Primary completion15 Jul 2024 (estimated)
  4. Study completion15 Oct 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04259944
Sponsor's protocol ID
IFOM-CPT005/2019/PO004
Other IDs
2019-002074-32, 2019
Status last verified
Sep 2023
First submitted
5 Feb 2020
Last updated
28 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Marsoni S, Montagut C, Pietrantonio F, Sartore-Bianchi A, Lazzari L, Bergamo F, Zampino MG, Tarazona N, Mandala M, Tamberi S, Elez E, Santos Vivas C, Luraghi P, Prisciandaro M, Tosi F, Ciardiello D, Vidal J, Segui V, Palazzo M, Maddalena G, Bencardino K, Taglialatela I, Guix M, Rulli E, Vettore V, Morano F, Isella C, Crisafulli G, Patelli G, Medico E, Bardelli A, Cervantes A, Torri V, Tabernero J, Siena S, Lonardi S. Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial. Nat Cancer. 2026 Sep 14. doi: 10.1038/s43018-026-01237-9. Online ahead of print.

    PubMed 42736431

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CAPOX, Capecitabine and FOLFIRI in people with Colon Cancer, run by IFOM ETS - The AIRC Institute of Molecular Oncology at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of post-surgery and post-adjuvant false negative cases after a double ctDNA-negative detection (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04259944, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.

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