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

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.

Trial Description

Primary Outcome:

  • Radiological response to pre-operative chemotherapy as assessed by RECIST v1.1
  • Biochemical response to pre-operative chemotherapy as assessed by plasmatic CEA measurement, change from baseline after 4 cycles of chemotherapy
  • Pathological response to pre-operative chemotherapy as assessed by Ryan and Rubbia Brandt Tumour Regression Grade (TRG) scores on resected tumours
  • Tumour response to pre-operative chemotherapy as assessed by change in circulating tumour DNA level, change from baseline
  • Histopathologic growth pattern as assessed by percent replacement, desmoplastic, and pushing features measured at the interface of liver metastasis and non tumoural liver
  • Post-operative minimal residual disease as assessed by circulating tumour DNA detection after tumour resection with curative intent
  • Time to radiological recurrence after tumour resection with curative intent
  • Time to biochemical recurrence as assessed by plasmatic CEA measurement, level above the upper limit occurring after tumour resection with curative intent
  • Time to tumour recurrence as assessed by detection or change in level of circulating tumour DNA after tumour resection with curative intent
Secondary Outcome:
  • Incidence and grade of FOLFOX-induced neuropathy, as assessed by Sensory Subscale of the NCI CTCAE scale, version 3
  • Incidence of allergic reaction to oxaliplatin diagnosed by treating physicians and requiring desensitization or change in chemotherapy regimen
  • Incidence of hospitalization for febrile neutropenia diagnosed by treating physicians
  • Ninety-day post-surgical complications, defined by Clavien Dindo grading system
  • Disease-specific survival after complete tumour resection
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, tumour tissue, and stool samples will allow investigation of circulating tumour 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.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society