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

NCT04566614 | Completed

• 1 other identifier: CCR 5292
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 1

Brief 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 and the subsequent recovery period.

Conditions

Neoplasm, Colorectal; Neoplasm of Lung; Neoplasm, Bladder; Neoplasms Pancreatic; Biliary Tract Neoplasms; Gastro Intestinal Stromal Tumour

Outcome Measures

Primary Outcomes (2)

• 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

  Throughout study completion, up to one year

• PREVAIL ctDNA Part 2 Study

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

  To run parallel for 12 months alongside the ACCESS implementation programme

Secondary Outcomes (20)

• Proportion of patients with a positive ctDNA result which identified a diagnosis and/or commenced treatment

  Throughout study completion, up to one year

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

  Throughout study completion, up to one year

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

  Throughout study completion, up to one year

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

  Throughout study completion, up to one year

• PREVAIL ctDNA Part 2 Study secondary end point 1a

  To run parallel for 12 months alongside the ACCESS implementation programme

Study Arms (7)

Biliary Tract Cohort

Patients 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

Other: ctDNA blood sampling

Bladder Cancer Cohort

Patients 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

Other: ctDNA blood sampling

Pancreatic Cancer Cohort

Patients 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

Other: ctDNA blood sampling

Gastrointestinal Stromal Tumour Cohort

Those 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

Other: ctDNA blood sampling

Lung Cancer Cohort

The 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)

Other: ctDNA blood sampling

Colorectal Cancer Cohort

Patients 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

Other: ctDNA blood sampling

Part 2 Cohort

Patients 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.

Interventions

ctDNA blood sampling OTHER

Screening/baseline blood sample to be analysed for ctDNA

Biliary Tract Cohort; Bladder Cancer Cohort; Colorectal Cancer Cohort; Gastrointestinal Stromal Tumour Cohort; Lung Cancer Cohort; Pancreatic Cancer Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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).
• Patients with an established histological diagnosis adequate to support standard of care treatment
• PART 2:
• Included in the ACCESS implementation programme
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Lung Neoplasms; Urinary Bladder Neoplasms; Pancreatic Neoplasms; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Biliary Tract Diseases

Study Officials

• Justin Mencel, MBBS

  Royal Marsden Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: September 28, 2020
• Study Start: June 18, 2020
• Primary Completion: July 31, 2023
• Study Completion: January 31, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Locations

GB (1)