Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients (eDetect-mCRC)

• ClinicalTrials.gov Identifier: NCT05068531
• Recruitment Status: Recruiting
• First Posted: October 6, 2021
• Last Update Posted: April 18, 2024
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Information provided by (Responsible Party): Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information

• First Submitted Date: September 2, 2021
• First Posted Date: October 6, 2021
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: September 1, 2022
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 24, 2021)

• Radiological response to pre-operative chemotherapy as assessed by RECIST v1.1 [ Time Frame: Approximately three months ]
• Biochemical response to pre-operative chemotherapy as assessed by plasmatic CEA measurement, change from baseline after 4 cycles of chemotherapy [ Time Frame: Approximately three months ]
• Pathological response to pre-operative chemotherapy as assessed by Ryan and Rubbia Brandt Tumor Regression Grade (TRG) scores on resected tumors [ Time Frame: Approximately three months ]
• Tumor response to pre-operative chemotherapy as assessed by change in circulating tumor DNA level, change from baseline [ Time Frame: Approximately three months ]
  Follow It assay, Canexia Health
• Histopathologic growth pattern as assessed by percent replacement, desmoplastic, and pushing features measured at the interface of liver metastasis and non tumoral liver [ Time Frame: Three to four months ]
• Post-operative minimal residual disease as assessed by circulating tumor DNA detection after tumor resection with curative intent [ Time Frame: Approximately 1 months after resection with curative intent ]
  Follow It assay, Canexia Health
• Time to radiological recurrence after tumor resection with curative intent [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to three years after tumor resection with curative intent ]
  Follow It assay, Canexia Health

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 24, 2021)

• Incidence and grade of FOLFOX-induced neuropathy, as assessed by Sensory Subscale of the NCI CTCAE scale, version 3 [ Time Frame: 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 [ Time Frame: Two to three months pre-operatively and during post-operative adjuvant chemotherapy ]
• Incidence of hospitalization for febrile neutropenia diagnosed by treating physicians [ Time Frame: Two to three months pre-operatively and during post-operative adjuvant chemotherapy ]
• Ninety-day post-surgical complications, defined by Clavien Dindo grading system [ Time Frame: 90 days after tumor resection ]
• Disease-specific survival after complete tumor resection [ Time Frame: Up to three years after tumor resection with curative intent ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients
• Official Title: A Prospective Observational Cohort Study for Early Detection of Treatment Failure in Metastatic Colorectal Cancer Patients Undergoing Systemic Chemotherapy and Liver Resection With Curative Intent
• 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

• 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.

• 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.
• Condition: Colorectal Cancer Metastatic
• Intervention: Not Provided

Study Groups/Cohorts

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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 24, 2021): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wiam Belkaid, PhD; 514-890-8000 ext 23242; wiam.belkaid.chum@ssss.gouv.qc.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05068531
• Other Study ID Numbers: 21.103
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Simon Turcotte, MD, MSc; CHUM

• PRS Account: Centre hospitalier de l'Université de Montréal (CHUM)
• Verification Date: April 2024