Clinical trial NCT05051592: Role of Circulating Tumour DNA Testing in Assessing for Alterations of Primary Anti-EGFR Resistance in RAS/RAF Wild-type Metastatic Colorectal Cancer Patients
Official title: Role of Circulating Tumour DNA (ctDNA) Testing in Assessing for Alterations of Primary Anti-Epidermal Growth Factor Receptor (EGFR) Resistance in RAS/RAF Wild-type Metastatic Colorectal Cancer Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Cancer
Keywords: ctDNA
anti_EGFR
RAS/RAF wild-type metastatic colorectal cancer
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2021-09-21
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed RAS/BRAF wild-type mCRC who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies will be recruited into the study. These are patients who are cared for at the National University Cancer Institute, Singapore (NCIS), and identified through the colorectal surgery, medical oncology and multidisciplinary CRC tumour board at NCIS.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Detection rate of alterations of anti-epidermal growth factor receptor primary resistance using Circulating tumour DNA
timeFrame: One timepoint, within 4 weeks prior to starting of anti-EGFR therapy
Secondary outcomes:
measure: Response rate
timeFrame: 1 year 6 months
measure: Progression-free survival
timeFrame: 1 year 6 months
measure: Overall survival
timeFrame: 1 year 6 months
measure: Adverse reactions experience by patient
timeFrame: 1 year 6 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Cheng Ean Chee
role: PRINCIPAL_INVESTIGATOR
References:
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