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Neoplasm, ColorectalPREVAILctDNANCT04566614

Preventing Viral Pandemic Associated Risk of Cancer Death Using Less Invasive Diagnostic Tests- Liquid Biopsies

An observational study of Neoplasm, Colorectal and Neoplasm of Lung, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate the feasibility of using ctDNA to support cancer diagnosis and risk stratification where invasive aerosol generating testing (and/or tissue biopsy) is challenging due to infection risk, technical impracticalities and resource limitations, such as during the COVID-19 pandemic… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ctDNA blood sampling
How many people
128 participants
Where
1 siteUnited Kingdom
Study dates
18 Jun 2020to 31 Jan 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with suspected malignancy for whom invasive biopsy for definitive histological diagnosis is challenging either due to COVID-19-related resource limitations, infection control or technical feasibility will be considered for this study

Who may be able to join

  • Participants aged ≥18 years old
  • Patients with suspected malignancies of early stage colorectal cancer (FIT intermediate and high risk), early and late stage pancreatic cancer, biliary tract cancer, gastro-intestinal stromal tumours, lung cancer or bladder cancer, without a definitive histological diagnosis (including those with inconclusive biopsy result) or
  • Patients with histological diagnosis of lung cancer without adequate tissue for NHS genomic test directory predictive biomarker testing
  • Ability to provide informed consent.
  • Patients with performance status suitable for oncological treatments (ECOG performance status 0-2).
  • Included in the ACCESS implementation programme
Show all 10Show fewer
  • Has detectable ctDNA on Guardant360© assay
  • Discussion at molecular tumour board and central multi-disciplinary meeting confirming ctDNA variant is supportive of diagnosis of PC/BTC (diagnostic or consistent with)
  • Performance status suitable for oncological treatment
  • Ability to provide informed consent

Who cannot join

  • Patients with an established histological diagnosis adequate to support standard of care treatment
  • PART 2:
  • Previously diagnosed invasive or haematological malignancy within the past 3 years
  • Outcome at the molecular tumour board not supportive of cancer diagnosis (possibly consistent or not consistent)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

The purpose of this study is to investigate the feasibility of using ctDNA to support cancer diagnosis and risk stratification where invasive aerosol generating testing (and/or tissue biopsy) is challenging due to infection risk, technical impracticalities and resource limitations, such as during the COVID-19 pandemic and the subsequent recovery period.

Read the detailed description

This is a prospective, single-centre cohort pilot study using ctDNA informed treatment decisions. If the pilot study is successful within certain tumour types then this protocol may be extended to investigate further the benefit of ctDNA informed treatment decision in those tumour types.

Patients with suspected malignancy for whom invasive biopsy for definitive histological diagnosis is challenging either due to COVID-19-related resource limitations, infection control or technical feasibility will be considered for this study. In this setting liquid biopsy may be used in lieu of tissue biopsy to facilitate treatment or may be used to prioritise standard of care invasive diagnostic tests. The former includes patients who require repeat biopsies for genomic analysis following non-informative results where these would inform standard of care treatment (i.e. NICE (National Institute for Health and Care Excellence)/Cancer Drug Fund (CDF) approved drugs). Tumour types included in this study are therefore those where invasive aerosol generating diagnostic tests such as bronchoscopy, gastrointestinal endoscopy (including endoscopic ultrasound (EUS)) are part of the standard diagnostic pathway and where capacity for these tests has become severely constrained during (and likely after) the COVID-19 pandemic. Tumour types affected include some suspected biliary tract, bladder, colorectal, GIST, lung and pancreatic cancers.

The study is planned to continue until a total of 144 patients have been enrolled. This is anticipated to take up to 12-18 months. Follow-up will continue until patients have diagnosis made (based on ctDNA result) and treatment decision made (deferred or immediate).

Potential patients will be identified in and will usually at the multidisciplinary team (MDT) meeting. They will give consent to participate in the trial and offered a liquid biopsy (ctDNA) in lieu of a tissue biopsy if considered suitable for PREVAIL - ctDNA. This may include patients who require repeat biopsies for further genomic analyses when repeat biopsies are not feasible where liquid biopsy may support prioritisation for invasive diagnostics earlier. ctDNA analysis will involve copy number variant detection and low coverage whole genomic sequencing. ctDNA gene panels have already been validated against tissue based molecular diagnostics for paediatrics (ct_PAED) and colorectal cancer (ct_GI).

This analysis will be performed in an accredited clinical diagnostic laboratory (Translational Research Laboratory, Institute of Cancer Research). Patients will be stratified for treatment or further investigation based on their ctDNA result (either positive or negative), suspected tumour type, radiological (including PREVAIL-imaging risk stratification pathway) and clinical characteristics.

PREVAIL ctDNA- Part 2 Study:

PREVAIL part 2 is a multi-centre, prospective study assessing the impact of Guardant360© liquid biopsy in patients with radiologically suspicious pancreatic cancer (PC) and biliary tract cancer (BTC)without histological confirmation of malignancy.

Liquid biopsies will be implemented into the routine diagnostic pathway across 6 RMP sites for patients with radiologically suspicious stage III/IV PC/BTC as part of the ACCESS implementation programme. Over 12 months, approximately 650 patients will be identified at individual sites by the local team when seen for an invasive procedure and referred in parallel to the Guardant360© test. These patients will proceed through an invasive diagnostic pathway as is standard of care and have a liquid biopsy as a new standard of care. Most patients will undergo both invasive tissue biopsy and liquid biopsy.

Patients with informative liquid biopsy result, but without a histological diagnosis of cancer (either due to inconclusive biopsy result or if the invasive procedure hasn't been performed) will be considered suitable for the study. Only patients with detectable ctDNA without histological confirmation will be suitable for this study (approximately ¼ of patients entering the ACCESS programme). The study is planned to run parallel to the ACCESS implementation programme and it aims to enrole 150 patients.

As part of this study, treatment may be recommended based on the liquid biopsy result. Patients with an invasive biopsy result which is suitable to guide treatment will not be eligible.

ctDNA results will be discussed at the molecular tumour board (MTB) to provide clinical context and validity of the genomic result. In addition, all patients will be discussed at a central upper gastrointestinal cancer multidisciplinary team meeting (MDM) to discuss treatment based on ctDNA results. Treating clinicians will have access to the MTB outcome and patients may be treated based on the ctDNA result in the context of symptoms, tumour markers, and imaging results as a complete diagnostic package.

Being tested
ctDNA blood sampling
Medical subject headings
Colorectal Neoplasms, Lung Neoplasms, Urinary Bladder Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ctDNA blood samplingOther

    Screening/baseline blood sample to be analysed for ctDNA

Study groups in NCT04566614
Study groupRoleWhat they receive
Biliary Tract CohortPatients with suspected biliary tract cancer will be offered ctDNA to support a diagnosis in patients with suspected early stage, locally advanced and advanced disease. This includes patients with tumours that are technically challenging to access with invasive biopsy or due to limitations in endoscopic ultrasound due to the COVID-19 pandemic. Patients with histological diagnosis will not be eligible for this study. Patients with suspected cancer will have ctDNA result (positive or negative) discussed at MDT in conjunction with PREVAIL-imaging risk stratification pathway to risk stratify in terms of cancer risk (low, intermediate and high risk), serum tumour markers and patient presentation which will dictate the appropriate treatment. Those with metastatic disease will have their treatment decision based on ctDNA result, radiology and patient characteristics after discussion between the treating clinician and patient
Receives: Other: ctDNA blood sampling
Bladder Cancer CohortPatients with suspected bladder cancer (localised and metastatic) will be offered ctDNA to support their diagnosis, in cases where cystoscopy and biopsy are difficult to obtain due to the COVID-19 pandemic. Patients with histological diagnosis will not be eligible for this study. A positive ctDNA result will be supportive of a diagnosis of bladder cancer, their treatment may be prioritised and decided based on this result in conjunction with radiological findings, patient presentation and after discussion between the treating physician and patient
Receives: Other: ctDNA blood sampling
Pancreatic Cancer CohortPatients with suspected pancreatic cancer will be offered ctDNA to support a diagnosis in patients with suspected early stage, locally advanced and advanced disease. This includes patients with tumours that are technically challenging to access with invasive biopsy or due to limitations in endoscopic ultrasound due to the COVID-19 pandemic. Patients with histological diagnosis will not be eligible for this study. Patients with suspected cancer will have ctDNA result (positive or negative) discussed at MDT in conjunction with PREVAIL-imaging risk stratification pathway to risk stratify in terms of cancer risk (low, intermediate and high risk), serum tumour markers and patient presentation which will dictate the appropriate treatment. Those with metastatic disease will have their treatment decision based on ctDNA result, radiology and patient characteristics after discussion between the treating clinician and patient
Receives: Other: ctDNA blood sampling
Gastrointestinal Stromal Tumour CohortThose with suspected Gastrointestinal Stromal Tumour Cohort (GIST) are eligible for this study. KIT and PDGFR mutation detected using ctDNA in conjunction with radiological features will be supportive of a diagnosis of GIST. This may allow for the use of directed targeted therapy, or prioritise surgical resection in some cases. Patients with histological diagnosis will not be eligible for this study. However, patients with inadequate tissue for KIT/PDGFR analysis will be eligible for PREVAIL-ctDNA to confirm the diagnosis of GIST and help guide treatment decisions
Receives: Other: ctDNA blood sampling
Lung Cancer CohortThe use of ctDNA in the diagnosis and adaptive management of patients with lung cancer is well established, however not funded by NHS. As aerosol-generating bronchoscopy procedures have reduced due to the COVID-19 pandemic, patients with suspected lung cancer may be offered ctDNA to support the diagnosis. A positive ctDNA result in conjunction with radiological findings will assist in prioritising those suitable for upfront surgical resection, radiotherapy or systemic anti-cancer treatment. It may provide sufficient genotypic information to guide standard of care targeted therapies (usually two tests are required - biopsy and then next generation sequencing of extracted DNA), including in patients without sufficient tissue for EGFR and ALK testing which can be detected using ctDNA. The use of ctDNA to guide treatment decisions in this cohort will not require signed consent as it is considered a standard approach (not yet NHS funded)
Receives: Other: ctDNA blood sampling
Colorectal Cancer CohortPatients with suspected colorectal cancer will often be referred following either suspicion on imaging or faecal immunochemical testing (FIT). FIT testing results will be used to prioritise patients for screening colonoscopy, in conjunction with the PREVAIL-imaging risk stratification pathway
Receives: Other: ctDNA blood sampling
Part 2 CohortPatients with suspected advanced pancreatic or biliary tract cancer who have ctDNA via the ACCESS implementation pathway. The results must be deemed consistent with or diagnostic of pancreatic/biliary tract cancer by the molecular tumour board, discussed at central MDT and the patient cannot have a histological diagnosis.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ctDNA detection rate within different cancer types (and overall)

    The primary endpoint, ctDNA detection rate, overall and within different cancer types will be presented as a proportion of patients with a positive ctDNA test out of those tested, with 90% confidence intervals

    Measured: Throughout study completion, up to one year

  2. PREVAIL ctDNA Part 2 Study

    Primary end point, Proportion of patients with detectable ctDNA which supports a diagnosis of malignancy and commence treatment

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

Secondary outcomes (20)
  1. Proportion of patients with a positive ctDNA result which identified a diagnosis and/or commenced treatment

    All secondary endpoints will be analysed in the patients diagnosed with suspected cancer, i.e. positive ctDNA result, unless stated. They will also be presented overall and by cancer type. The proportion of patients with positive ctDNA result which identified a diagnosis and/or commenced treatment will be presented as a proportion with 90% confidence intervals

    Measured: Throughout study completion, up to one year

  2. Proportion of patients with a positive ctDNA result which assisted in prioritising invasive diagnostic tests

    Proportion of patients with positive ctDNA result which assisted in prioritising invasive diagnostic tests will be presented as a proportion with 90% confidence intervals

    Measured: Throughout study completion, up to one year

  3. The association of ctDNA result (positive versus negative) and the PREVAIL-imaging pathway scoring result

    The association between ctDNA result (positive versus negative) and the PREVAIL-imaging pathway scoring result will be assessed descriptively by presenting cross-tabulations and relevant proportions

    Measured: Throughout study completion, up to one year

  4. Estimation of the cost of liquid biopsy in lieu of tissue biopsy as compared to standard of care investigations and treatments prioritisation

    Simple estimation of the cost of liquid biopsy in lieu of tissue biopsy as compared to standard of care investigations and treatments prioritisation will be performed

    Measured: Throughout study completion, up to one year

  5. PREVAIL ctDNA Part 2 Study secondary end point 1a

    Treatment response objective response rate

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  6. PREVAIL ctDNA Part 2 Study secondary end point 1b

    Progression free survival

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  7. PREVAIL ctDNA Part 2 Study secondary end point 1c

    Overall survival

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  8. PREVAIL ctDNA Part 2 Study secondary end point 2

    Proportion of patients who undergo a repeated invasive procedure

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  9. PREVAIL ctDNA Part 2 Study secondary end point 3a- comparison with NHS targets

    Comparison of diagnostic pathway duration with NHS faster Diagnostic Standard (FDS)

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  10. PREVAIL ctDNA Part 2 Study secondary end point 3b- comparison with NHS targets

    Comparison of diagnostic pathway duration with 62 day wait target

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  11. PREVAIL ctDNA Part 2 Study secondary end point 4a

    Type of complications from invasive diagnostic procedures

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  12. PREVAIL ctDNA Part 2 Study secondary end point 4b

    Frequency of complications from invasive diagnostic procedures

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  13. PREVAIL ctDNA Part 2 Study secondary end point 4c

    Severity of complications from invasive diagnostic procedures

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  14. PREVAIL ctDNA Part 2 Study secondary end point 5

    Number and type of invasive procedures performed

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  15. PREVAIL ctDNA Part 2 Study secondary end point 5b

    Number of histopathology reviews

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  16. PREVAIL ctDNA Part 2 Study secondary end point 5c

    Number of tissue based NGS performed

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  17. PREVAIL ctDNA Part 2 Study secondary end point 6a

    Healthcare costs associated with diagnostic pathway

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  18. PREVAIL ctDNA Part 2 Study secondary end point 6b

    Cost per-quality adjusted-life-year of diagnostic pathway

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  19. PREVAIL ctDNA Part 2 Study secondary end point 6c

    Number of hospital visits in diagnostic pathway

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

  20. PREVAIL ctDNA Part 2 Study secondary end point 6d

    Length of hospital stay during diagnostic pathway

    Measured: To run parallel for 12 months alongside the ACCESS implementation programme

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2020
  2. Study start18 Jun 2020
  3. Primary completion31 Jul 2023
  4. Study completion31 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04566614
Sponsor's protocol ID
CCR 5292
Acronym
PREVAILctDNA
Status last verified
Apr 2025
First submitted
2 Jun 2020
Last updated
6 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

An observational study of Neoplasm, Colorectal and Neoplasm of Lung, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ctDNA detection rate within different cancer types (and overall) (time frame: Throughout study completion, up to one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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