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

Primary Purpose

Colon Cancer

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

CAPOX

Capecitabine

FOLFIRI

About this trial

This is an interventional treatment trial for Colon Cancer focused on measuring liquid biopsy, colon cancer, adjuvant treatment, ctDNA, colorectal cancer, CAPOX, FOLFIRI, CAPE

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Ospedale Policlinico San Martino IRCCS
Fondazione IRCCS Istituto Nazionale dei Tumori
Istituto Europeo di Oncologia IRCCS
Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda
Istituto Oncologico Veneto IRCCS
Ospedale Santa Maria della Misericordia
AULS della Romagna
Hospital Moises Broggi
University Hospital del Mar
Vall d'Hebron Institute of Oncology
INCLIVA Biomedical Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Liquid Biopsy-Guided Adjuvant Treatment

Arm Description

A 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Disease-Free Survival (DFS)

Overall Survival (OS)

Safety and tolerability according to CTCAE version 5.0

Assessment of QLQ-C30 and CR-29 EORTC questionnaires

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

Full Information

NCT ID

NCT04259944

First Posted

February 5, 2020

Last Updated

September 26, 2023

Sponsor

IFOM ETS - The AIRC Institute of Molecular Oncology

Collaborators

Guardant Health, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04259944

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: the PEGASUS Trial

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 16, 2020 (Actual)

Primary Completion Date

July 15, 2024 (Anticipated)

Study Completion Date

October 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

IFOM ETS - The AIRC Institute of Molecular Oncology

Collaborators

Guardant Health, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer

Keywords

liquid biopsy, colon cancer, adjuvant treatment, ctDNA, colorectal cancer, CAPOX, FOLFIRI, CAPE

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Liquid Biopsy-Guided Adjuvant Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

CAPOX

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

FOLFIRI

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of post-surgery and post-adjuvant false negative cases after a double ctDNA-negative detection

Description

Cases that become positive at subsequent interventional LB or that experience radiological relapse

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Disease-Free Survival (DFS)

Time Frame

2 & 3 years

Title

Overall Survival (OS)

Time Frame

5 years

Title

Safety and tolerability according to CTCAE version 5.0

Time Frame

2 years

Title

Assessment of QLQ-C30 and CR-29 EORTC questionnaires

Time Frame

2 years

Title

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

Time Frame

2 & 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sara Lonardi, MD

Organizational Affiliation

Istituto Oncologico Veneto IRCCS

Official's Role

Study Chair

Facility Information:

Facility Name

Ospedale Policlinico San Martino IRCCS

City

Genova

Country

Italy

Facility Name

Fondazione IRCCS Istituto Nazionale dei Tumori

City

Milan

Country

Italy

Facility Name

Istituto Europeo di Oncologia IRCCS

City

Milan

Country

Italy

Facility Name

Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda

City

Milan

Country

Italy

Facility Name

Istituto Oncologico Veneto IRCCS

City

Padova

Country

Italy

Facility Name

Ospedale Santa Maria della Misericordia

City

Perugia

ZIP/Postal Code

06132

Country

Italy

Facility Name

AULS della Romagna

City

Ravenna

ZIP/Postal Code

48121

Country

Italy

Facility Name

Hospital Moises Broggi

City

Sant Joan Despí

State/Province

Barcelona

ZIP/Postal Code

08970

Country

Spain

Facility Name

University Hospital del Mar

City

Barcelona

Country

Spain

Facility Name

Vall d'Hebron Institute of Oncology

City

Barcelona

Country

Spain

Facility Name

INCLIVA Biomedical Research Institute

City

Valencia

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

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

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