Feasibility Study of Blood Biomarker Identification in Cervical Cancer
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexFemale
Age18+
SponsorQueensland Centre for Gynaecological Cancer
About this trial
This study aims to explore whether a simple blood test can be used to help detect and monitor cervical cancer. The investigators are studying tiny fragments and particles found in blood, called cell-free DNA (cfDNA) and extracellular vesicles (EVs), to determine whether these can act as early warning signs (biomarkers) of cervical cancer.
Cell-free DNA (cfDNA) refers to tiny fragments of genetic material (DNA) that are naturally released from cells into the bloodstream when cells die or renew. Cell-free DNA circulates naturally in the blood. In people with cancer, some of the cfDNA originates from cancer cells; this component is called circulating tumour DNA (ctDNA). Analysis of cfDNA can detect signs of cancer, such as specific genetic changes or pieces of viral DNA, including human papillomavirus (HPV) DNA, without requiring removal of tissue from the cervix.
Extracellular vesicles (EVs) are very small "packages" released by cells into the blood and other body fluids. EVs carry messages between cells and contain important information such as proteins, fats, and genetic material, including RNA. In cancer, tumour cells release EVs that reflect tumour behaviour and activity. Analysis of EVs can provide information about cancer growth and response to treatment.
Together, cfDNA and EVs can act as tiny messengers or "fingerprints" of biological processes occurring inside the body. Analysis of cfDNA and EVs in blood samples may support the development of a simple, less invasive, more comfortable, and more accessible approach to detecting and monitoring cervical cancer compared with current screening and diagnostic methods. A blood test could also assist doctors in monitoring treatment response or detecting early signs of recurrence without requiring a surgical biopsy.
The expected outcomes of this study are to identify specific patterns or "signatures" in extracellular vesicles (EVs) and cell-free DNA (cfDNA) found in blood samples. These signatures could help to:
Detect cervical cancer earlier, before symptoms appear or the disease progresses.
Monitor treatment response in real time without the need for invasive tests. Predict whether cervical cancer might recur or spread after treatment. Support more personalised care by helping doctors select the most suitable treatment for each participant.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Females, over 18 years, with histologically confirmed squamous cell carcinoma or adenocarcinoma of the cervix (stage 1a to 4b)
Undergo intensive primary surgical treatment, radiotherapy (RT) or chemoradiotherapy (CRT).
Signed written informed consent
Disqualifiers
Unable to provide informed consent
Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
Prior malignancies <5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma in situ.
Trial population
100 patients with histologically confirmed squamous cell carcinoma or adenocarcinoma of the cervix (stage 1a to 4b).
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Blood Sample Collection
Procedure/SurgeryApproximately 40 mL of blood will be collected at baseline, approximately 8 weeks (±14 days) after surgery or within 14 days following completion of radiotherapy/chemoradiotherapy, and 6 months (±14 days) post-baseline. Blood samples will be processed for isolation and analysis of cell-free DNA (cfDNA), extracellular vesicles (EVs), and germline DNA.
cfDNA and Extracellular Vesicle Biomarker Analysis
Other interventionBlood-derived cell-free DNA (cfDNA) and extracellular vesicles (EVs) will be isolated and characterised using prespecified laboratory methods. cfDNA will be quantified, quality assessed, and may undergo sequencing. EVs will be characterised using methods including nanoparticle tracking analysis, transmission electron microscopy, western blotting, proteomics, and miRNA sequencing. Biomarker profiles will be evaluated in relation to disease stage, treatment response, and disease outcomes.
Patient-Reported Outcome and Quality-of-Life Assessment
Other interventionParticipants will complete patient-reported outcome and quality-of-life questionnaires at baseline, approximately 8 weeks after surgery or completion of radiotherapy/chemoradiotherapy, and 6 months post-baseline. Assessments include the FACT-Cx, EQ-5D-5L, and self-reported lower-extremity lymphoedema questionnaires.
Tumour Tissue Biomarker Analysis
Other interventionFormalin-fixed paraffin-embedded (FFPE) tumour tissue obtained during routine diagnostic biopsy or surgery will be retrieved from pathology laboratories where available. No research-specific tumour biopsy or surgery will be performed. Tumour tissue may undergo DNA extraction and sequencing for comparison with blood-derived DNA and other prespecified translational analyses.
Treatment groups
100 Participants
are divided into 1 treatment groupGroup A: Patients with Cervical Cancer4 interventions
Trial outcomes
Primary outcomes
1
Proportion of participants with successful blood collection and analysable cfDNA and EVs
Percentage of enrolled participants for whom blood is successfully collected and both cell-free DNA (cfDNA) and extracellular vesicles (EVs) are successfully isolated and meet prespecified laboratory quality-control criteria for the planned downstream analyses. Feasibility will be assessed at each of the three scheduled blood-collection time points.
Time frame
Baseline; approximately 8 weeks (±14 days) after surgery or within 14 days following completion of radiotherapy/chemoradiotherapy; and 6 months (±14 days) post-baseline.Secondary outcomes
1
Proportion of eligible patients who consent to participate
Percentage of eligible patients with cervical cancer who provide informed consent and enrol in the study among all eligible patients approached for participation.
Time frame
At study screening/enrolment.2
Proportion of cfDNA samples meeting prespecified analytical quality criteria
Percentage of collected plasma samples from which cell-free DNA (cfDNA) is successfully extracted and meets prespecified quality-control criteria for downstream analysis. cfDNA will be quantified and quality assessed, including assessment of yield, integrity, and suitability for planned molecular analyses and/or sequencing.
Time frame
Baseline; approximately 8 weeks (±14 days) after surgery or within 14 days following completion of radiotherapy/chemoradiotherapy; and 6 months (±14 days) post-baseline.3
Proportion of extracellular vesicle samples meeting prespecified analytical quality criteria
Percentage of collected plasma/serum samples from which extracellular vesicles (EVs) are successfully isolated and meet prespecified quality-control criteria for downstream analysis. EV quantity and characteristics will be evaluated using methods including nanoparticle tracking analysis, transmission electron microscopy, and assessment of positive and negative EV markers by western blotting.
Time frame
Baseline; approximately 8 weeks (±14 days) after surgery or within 14 days following completion of radiotherapy/chemoradiotherapy; and 6 months (±14 days) post-baseline.4
Association between baseline cfDNA profiles and cervical cancer stage
Association between baseline cell-free DNA (cfDNA) characteristics and cervical cancer stage (FIGO stage IA-IVB). Prespecified cfDNA measures and/or molecular signatures obtained from plasma will be evaluated for differences across disease stages. Where applicable, tumour tissue and germline DNA sequencing data will be used as reference controls.
Time frame
BaselineSponsors and contacts
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Source ClinicalTrials.gov