None listed
Conditions
Brief summary
The purpose of this study is to see if the approach of using a blood test called a ‘liquid biopsy’ multiple times throughout the patient journey can improve the management of lung cancer by successfully guiding treatment. We will assess if it is possible to incorporate liquid biopsy into the routine care of Australians with lung cancer, including evaluating the clinical benefits to patients and the economic impact to the health system. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with advanced non-small cell lung cancer and you have received at least one previous targeted cancer treatment. Additional health checks may also be conducted by the study doctors to ensure you are able to take part in this study. Study details: All participants who choose to enroll in this study will be asked to provide a blood sample for molecular testing (liquid biopsy). The liquid biopsy test analyses fragments of DNA released from a person's cancer into their blood, known as circulating tumour DNA (ctDNA). This helps doctors to understand how a person's cancer has changed over time. The liquid biopsy results will be reviewed be reviewed by a board of experts. They will make treatment recommendations based on the liquid biopsy results. These will be provided to the participant's treating doctor, for discussion with the participant. Decisions for treatment are made by the participant and their treating doctor. Options may include a clinical research study, treatment(s) available through special access programs, and/or standard of care treatment that is routinely available. Participants will be asked to provide blood samples multiple times over a period of up to 4 years, including at study entry, each time a new treatment is started, and each time a treatment stops working. If a previous tissue sample is available or will be taken, e.g. during surgery, this may also be tested for new changes. Participants will also be asked to complete questionnaires throughout the study for up to 4 years after they enroll. It is hoped this research will determine whether adding liquid biopsy into the routine care of Australians with lung cancer is achievable, the economic costs and value of adding this procedure and to identify possible benefits to individuals with lung cancer by finding new targeted treatments for them.
Interventions
Molecular profiling using plasma ctDNA analysis to identify actionable biomarkers that may be used to guide therapy. After failure of molecularly-targeted therapy, participants will undergo liquid biopsy to obtain plasma for ctDNA analysis after patient consent and assessment of suitability for the study. CtDNA analysis will be performed using the multigene NGS panels ctTSO500 or Foundation One CDX, and will include over 300 genes that may be related to lung cancer, including EGFR, KRAS, BRAF, A
Molecular profiling using plasma ctDNA analysis to identify actionable biomarkers that may be used to guide therapy. After failure of molecularly-targeted therapy, participants will undergo liquid biopsy to obtain plasma for ctDNA analysis after patient consent and assessment of suitability for the study. CtDNA analysis will be performed using the multigene NGS panels ctTSO500 or Foundation One CDX, and will include over 300 genes that may be related to lung cancer, including EGFR, KRAS, BRAF, ALK and ROS1. Where tissue biopsies are taken for routine clinical care, the tissue will also be genomically analysed. Results from blood and/or tissue will be curated and reviewed by the Molecular Tumour Board (MTB), and the MTB treatment recommendations will be sent to the referring clinician. The MTB will not make treatment decisions. All treatment decisions will be made by the treating clinician and the participant. All members of the MTB are trained by qualification and experience to make treatment recommendations based on genomic profiling results. The members of the MTB include data scientists, clinicals pathologists and medical oncologists. The members of the MTB may be affiliated with hospitals around Australia, including for example the Peter MacCallum Cancer Centre. Treatment is at the treating clinician’s discretion. The molecular findings may be used to enroll participants in therapeutic trials, or obtain targeted treatments through special access programs, or participants may receive standard of care (SOC) treatment. Liquid biopsy performed at study entry or at the time of subsequent disease progression is intended to identify new targets/applicable therapies. Six weeks (± 2 weeks) after commencement of systemic therapy, blood will be collected for repeat liquid biopsy and for future translational studies and disease monitoring. Liquid biopsy performed 6 weeks after commencement of systemic therapy is intended to assess response to the current therapy (e.g. ctDNA clearance is correlated with better outcomes than non-clearance). When participants develop subsequent disease progression, they may undergo repeat liquid biopsy to provide recommendations for next line therapy. This is an iterative process that can be repeated until participants are no longer suitable to receive further therapy. There is no specific time limit of review for subsequent disease progression after initial liquid biopsy. The only limitation is the duration of study funding (the grant is for 4 years of testing and data collection), after which no further testing will be performed. If tissue biopsy is clinically indicated, the tissue will also be genomically analysed. The reviewing Human Research Ethics Committee (HREC) determined that this study is a device trial, as ctDNA analysis is being used to provide possible treatment recommendations to the treating clinicians of study participants. Treatment is at the treating clinician’s discretion. The reviewing HREC approved the study title to include the description of 'Observational', and approved the study as a device trial.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults aged 18 years and older with a diagnosis of advanced NSCLC 2. Known oncogenic driver (including but not limited to EGFR, KRAS, BRAF, MET exon 14 skipping mutations or ALK, ROS1, RET, NTRK, NRG1 fusions) 3. Previously received treatment with a genomically-targeted therapy (e.g. a tyrosine kinase inhibitor (TKI), antibody or molecularly-targeted antibody-drug conjugate (ADC)). Targeted therapy is not required to be the most recent treatment - any line is acceptable. 4. Clinical or radiological diagnosis of disease progression or intolerance 5. ECOG performance status 0, 1 or 2 within 7 days prior to site-based registration or remote referral 6. Able to provide written or electronic informed consent to participate in molecular profiling and linkage to Medicare data. Consent by remote referral is not suitable for participants with low literacy, insufficient English, or limited vision. 7. No history of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to this study and of low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ without evidence of disease 8. Willing and able to comply with study requirements.
Exclusion criteria
1. Serious medical or psychiatric conditions that might limit the ability of the participant to comply with the protocol
Outcome results
None listed