Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients

NCT ID: NCT05068531

Last Updated: 2024-04-18

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2026-10-31

Brief Summary

In North America, colorectal cancer patients with resectable liver-restricted metastases (mCRC-LR) are treated with approximately 6 months of preoperative systemic multi-agent chemotherapy. Actuarial data however supports that approximately 20% of mCRC-LR patients can be cured without as much systemic chemotherapy. Prospective phase II-III trials also support that awaiting recurrence to initiate further metastases-targeted or systemic treatment may provide patients with longer overall survival while avoiding toxicities in those without recurrence.

Detailed Description

The general objective of this single-centre, prospective observational cohort study in 100 mCRC-LR patients treated with curative intent along standard of care (SOC), is to obtain real-world data on administered therapies, selected complications, and oncological outcomes, while longitudinally collecting biospecimens to enable correlative research investigating early biological markers of treatment resistance and recurrence.

Cryopreservation of sequential blood derivatives, tumor tissue, and stool samples will allow investigation of circulating tumor DNA (ctDNA), T-cell receptor repertoire, somatic cancer mutations, immune and other gene expression, gut microbiome, and soluble factors.

The first biological marker that will be investigated in correlative research will be longitudinal measurements of ctDNA targeting 30 oncogenes, 23 axons, and 146 hotspots (Follow It assay, Canexia Health). Additional biological markers will be defined in subsequent amendments to this protocol.

The results are expected to provide important insights for the design of future trials investigating ways to personalize therapy, such as to: a) avoid the unnecessary use of neoadjuvant or adjuvant systemic chemotherapy, b) avoid morbid hepatectomies in patients unlikely to benefit, c) test novel preoperative therapies in patients more likely to benefit, and d) modulate the intensity of follow-up.

Conditions

Colorectal Cancer Metastatic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Observational

We plan to recruit up to 100 mCRC patients with baseline resectable liver-restricted metastases (mCRC-LR) without evidence of extra-hepatic metastases, with primary tumor already or to be resected (metachronous or synchronous disease), planned to receive upfront FOLFOX-based preoperative neoadjuvant systemic chemotherapy, who achieved no-evidence of disease (NED) in the abdomen by standard imaging.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Male or female patients (≥18 years of age at the time of consent);

2. Stage IV colon or rectal adenocarcinoma with liver-restricted metastasis(es) for whom partial hepatectomy with curative intent is planned;

3. Instead of, or in addition to, partial hepatectomy, liver metastases may be ablated by needle radio frequency or microwave; in case of a solitary liver metastasis, three core-needle biopsies are provided for research at time of the procedure and prior to tissue destruction;

4. Patients may undergo planned two-stage partial hepatectomies;

5. Patients may have at baseline lung micro nodules or intra-abdominal enlarged nodes or nodules of unknown nature, not considered as extra-hepatic metastases in the opinion of the investigator;

6. Patients who are scheduled to receive FOLFOX-based pre-hepatectomy may receive any additional combined agents, such as and not limited to Irinotecan, anti-EGFR, and anti-VEGF drugs;

7. Patients are willing and able to provide serial blood samples, tumor and adjacent tissues, and stool samples for research;

8. The timing and specific treatments of the primary colon or rectal tumor is per SOC, at the discretion of the treating physician, including the use of pre-operative radiotherapy for rectal cancer;

9. Patients may receive post-operative adjuvant chemotherapy per SOC, at the discretion of the treating physician;

10. Patients must consent to the Exactis Personalized my Treatment registry.

Exclusion Criteria

1. Pregnant or breastfeeding patients,

2. Hereditary colorectal cancer (e.g., familial colonic polyposis or Lynch syndrome), and

3. Presence of concurrent other cancer(s).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon Turcotte, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

CHUM

Locations

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Wiam Belkaid, PhD

Role: CONTACT

wiam.belkaid.chum@ssss.gouv.qc.ca

514-890-8000 ext. 23242

Facility Contacts

Wiam Belkaid, PhD

Role: primary

wiam.belkaid.chum@ssss.gouv.qc.ca

514-836-3273 ext. 23242

Other Identifiers

21.103

Identifier Type: -

Identifier Source: org_study_id