Post-Surgical Liquid Biopsy - Guided Treatment of Stage Iii and High-Risk Stage Ii Colon Cancer Patients - the Pegasus Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Sep 2024 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AIRC · Guardant Health

External identifiers

EU CT number

2024-517704-10-00

EudraCT number

2019-002074-32

ClinicalTrials.gov

NCT04259944

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis, Efficacy

The primary objective is to study the feasibility of using liquid biopsy to guide the post-surgical clinical management of stage III and high-risk stage II (T4N0) MSS colon cancer patients.
Feasibility is defined as the ability of at least two subsequent post-surgical negative ctDNA determination to identify patients that will be NED (without radiologic evidence of metastasis) 2 years after surgery.

Secondary objectives 4

1. To compare the DFS and OS rates at 2,3 and 5 years in a cohort of 140 stage III and high-risk stage II (only T4N0) MSS colon cancer patients treated post-surgically with a liquid biopsy-guided strategy, with the DFS and OS rates of a 1:3 phenotypically matched cohort of the TOSCA trial treated with FOLFOX/CAPOX either at 3 or 6 months.
2. To compare the safety profile in a cohort of 140 stage III and high-risk stage II (only T4N0) MSS colon cancer patients treated with a liquid biopsyguided strategy, with the safety profile of 1:3 phenotypically matched cohort of the TOSCA trial treated with FOLFOX/CAPOX either at 3 or 6 months.
3. To validate LB seroconversion (i.e. negativization of ctDNA detection upon treatment administration) as a proxy of therapy efficacy and to compare its performance with CEA testing whenever CEA levels are above the normal values.
4. To study the Quality of Life of patients in a cohort of 140 stage III and highrisk stage II (only T4N0) MSS colon cancer patients treated post-surgically with a liquid biopsy-guided strategy.

Conditions and MedDRA coding

Colon cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Pegasus trial written informed consent.
2. Age ≥ 18 years.
3. 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.
4. Availability of the original FFPE tumor tissue.
5. Availability of plasma collected prior to surgery.
6. Acceptance to undergo at least all the interventional liquid biopsies.
7. ECOG performance status 0-1.
8. Normal organ functions.
9. Women with childbearing potential should complete a pregnancy test and be willing to use highly effective contraceptive methods.

Exclusion criteria 16

1. Patients having a MSI-H/MMRd tumor are excluded from the study (test done according to standard clinical practice).
2. 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.
3. Had an incomplete diagnostic colonoscopy and/or polyps removal.
4. 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).
5. Current or recent treatment with another investigational drug or participation in another investigational study.
6. Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
7. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
8. Inadequate contraception (male or female patients) if of childbearing or procreational potential.
9. Clinically relevant cardiovascular disease.
10. Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
11. Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
12. Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant.
13. Has a known DPD (DihydroPyrimidine Dehydrogenase) deficiency.
14. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
15. 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.
16. Has a known history of active TB (Bacillus Tuberculosis).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of post-surgery false negative cases after a double ctDNA-negative detection, defined as cases that become positive at subsequent interventional LB and/or that experience radiological relapse within 2 years.

Secondary endpoints 4

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Sponsor organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Address

Via Adamello 16

City

Milan

Postcode

20139

Country

Italy

Scientific contact point

Organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Contact name

Silvia Marsoni

Public contact point

Organisation

IFOM Istituto Fondazione Di Oncologia Molecolare Ets In Breve Ifom Ets

Contact name

Silvia Marsoni

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications