Role of Circulating Tumour DNA Testing in Assessing for Alterations of Primary Anti-EGFR Resistance in RAS/RAF Wild-type Metastatic Colorectal Cancer Patients

• Conditions: Colorectal Cancer

• Registration Number: NCT05051592
• Lead Sponsor: National University Hospital, Singapore

Brief Summary

The study aims to explore the clinical utility of circulating tumour DNA (ctDNA) in assessing for alterations of anti-epidermal growth factor receptor (EGFR) primary resistance in RAS and BRAF wild-type metastatic colorectal cancer (CRC) patients treated with anti-EGFR monoclonal antibodies (cetuximab / panitumumab) in combination with fluorouracil (FU)-doublet chemotherapy.

Detailed Description

A single blood sample (20mL) will be collected after the patient has given informed consent. The blood sample will be collected within 4 weeks prior to the patient starting chemotherapy. Blood samples collected will be processed in accordance with the Guardant360 Clinical Blood Collection Kit instructions (Guardant Health, Inc.).

Patient outcomes with respect to response rate, progression-free survival, overall survival, toxicities and other co-morbid conditions will be ascertained by medical record review conducted by the study personnel. Prospective clinical data that will be collected include: patient demographics, tumor stage and pathological tumor characteristics at diagnosis, laboratory data at diagnosis and serial pre-specified time points, imaging outcomes, chemotherapy information, date of recurrence, and date and cause of death.

Although the data will be censored at the study end-points, the patient's medical record will be reviewed indefinitely to follow the health outcomes.

Study Timeline

• Study Start: 2021-03-26
• Status Verified: 2021-09
• Study First Submitted: 2021-09-08
• Study First Submitted QC: 2021-09-19
• Study First Posted: 2021-09-21
• Last Update Submitted: 2021-09-28
• Last Update Posted: 2021-10-05
• Primary Completion: 2022-09
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Patients with newly diagnosed stage IV colon or rectal cancer who are RAS/BRAF wild-type by routine tumor profiling and who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies. Prior treatment with adjuvant therapy is allowed if completed more than 6 months prior to relapse of disease.

Exclusion Criteria

• Pregnant women will be excluded from the study.
• Patient unable to give informed consent will be excluded from the study.
• Patients who have previously received chemotherapy in the metastatic setting.
• Patients who have previously received adjuvant chemotherapy less than 6 months prior to relapse of metastatic disease.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detection rate of alterations of anti-epidermal growth factor receptor primary resistance using Circulating tumour DNA	One timepoint, within 4 weeks prior to starting of anti-EGFR therapy	ctDNA analysis will be carried out using Guardant360 platform to identify subgroup of patients who have primary resistance to anti-EGFR therapy.

Secondary Outcome Measures

Name	Time	Method
Response rate	1 year 6 months	Response rate to treatment received as per standard care.
Progression-free survival	1 year 6 months	The time from commencement of cancer treatment to disease progression or death from any cause.
Overall survival	1 year 6 months	The length of time from start of treatment to death.
Adverse reactions experience by patient	1 year 6 months	Toxicities in patients who have primary resistance to anti-EGFR therapy will be collected and analysed.

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore