Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients

NCT05068531 | Recruiting DMC

• 1 other identifier: 21.103
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic

Keywords

Real world data; Observational study; Circulating tumor DNA; Microbiome; Tumor immunology; Metastatic colorectal cancer; Liver metastasis; Biomarker

Outcome Measures

Primary Outcomes (9)

• Radiological response to pre-operative chemotherapy as assessed by RECIST v1.1

  Approximately three months

• Biochemical response to pre-operative chemotherapy as assessed by plasmatic CEA measurement, change from baseline after 4 cycles of chemotherapy

  Approximately three months

• Pathological response to pre-operative chemotherapy as assessed by Ryan and Rubbia Brandt Tumor Regression Grade (TRG) scores on resected tumors

  Approximately three months

• Tumor response to pre-operative chemotherapy as assessed by change in circulating tumor DNA level, change from baseline

  Follow It assay, Canexia Health

  Approximately three months

• Histopathologic growth pattern as assessed by percent replacement, desmoplastic, and pushing features measured at the interface of liver metastasis and non tumoral liver

  Three to four months

• Post-operative minimal residual disease as assessed by circulating tumor DNA detection after tumor resection with curative intent

  Follow It assay, Canexia Health

  Approximately 1 months after resection with curative intent

• Time to radiological recurrence after tumor resection with curative intent

  Up to three years after tumor resection with curative intent

• Time to biochemical recurrence as assessed by plasmatic CEA measurement, level above the upper limit occurring after tumor resection with curative intent

  Up to three years after tumor resection with curative intent

• Time to tumor recurrence as assessed by detection or change in level of circulating tumor DNA after tumor resection with curative intent

  Follow It assay, Canexia Health

  Up to three years after tumor resection with curative intent

Secondary Outcomes (5)

• Incidence and grade of FOLFOX-induced neuropathy, as assessed by Sensory Subscale of the NCI CTCAE scale, version 3

  Two to three months pre-operatively and during post-operative adjuvant chemotherapy

• Incidence of allergic reaction to oxaliplatin diagnosed by treating physicians and requiring desensitization or change in chemotherapy regimen

  Two to three months pre-operatively and during post-operative adjuvant chemotherapy

• Incidence of hospitalization for febrile neutropenia diagnosed by treating physicians

  Two to three months pre-operatively and during post-operative adjuvant chemotherapy

• Ninety-day post-surgical complications, defined by Clavien Dindo grading system

  90 days after tumor resection

• Disease-specific survival after complete tumor resection

  Up to three years after tumor resection with curative intent

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Male or female patients (≥18 years of age at the time of consent);
• Stage IV colon or rectal adenocarcinoma with liver-restricted metastasis(es) for whom partial hepatectomy with curative intent is planned;
• 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;
• Patients may undergo planned two-stage partial hepatectomies;
• 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;
• 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;
• Patients are willing and able to provide serial blood samples, tumor and adjacent tissues, and stool samples for research;
• 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;
• Patients may receive post-operative adjuvant chemotherapy per SOC, at the discretion of the treating physician;
• Patients must consent to the Exactis Personalized my Treatment registry.

You may not qualify if:

• Pregnant or breastfeeding patients,
• Hereditary colorectal cancer (e.g., familial colonic polyposis or Lynch syndrome), and
• Presence of concurrent other cancer(s).

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Serial blood samples processed to obtain plasma for ctDNA and soluble factor research, buffy coat for genomic research, and mononuclear cells for live cells immune assays; * Tumor samples processed to allow genomic, proteomic and live cell research; * Adjacent non-tumoral tissue to allow genomic, proteomic and live cell research; * Stool samples at baseline and post neoadjuvant chemotherapy to allow metagenomics research.

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Simon Turcotte, MD, MSc

  CHUM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wiam Belkaid, PhD

CONTACT

514-890-8000; wiam.belkaid.chum@ssss.gouv.qc.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: October 6, 2021
• Study Start: September 1, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

CA (1)