Clinical Trials /

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

NCT04259944

Description:

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.

Related Conditions:
  • Colon Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: IFOM-CPT005/2019/PO004
  • NCT ID: NCT04259944

Conditions

  • Colon Cancer

Interventions

DrugSynonymsArms
CAPOXLiquid Biopsy-Guided Adjuvant Treatment
CapecitabineLiquid Biopsy-Guided Adjuvant Treatment
FOLFIRILiquid Biopsy-Guided Adjuvant Treatment

Purpose

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 (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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • CAPOX
  • Capecitabine
  • FOLFIRI

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of post-surgery and post-adjuvant false negative cases after a double ctDNA-negative detection
Time Frame:2 years
Safety Issue:
Description:Cases that become positive at subsequent interventional LB or that experience radiological relapse

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:IFOM, The FIRC Institute of Molecular Oncology

Trial Keywords

  • liquid biopsy
  • colon cancer
  • adjuvant treatment
  • ctDNA

Last Updated

February 7, 2020