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

Biliary Tract Neoplasms Clinical Trial

— PREVAILctDNA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04566614
• Other study ID #: CCR 5292
• Status: Recruiting
• Start date: June 18, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2023
• Source: Royal Marsden NHS Foundation Trust
• Contact: Naureen Starling, MBBS MRCP MD
• Phone: 0208664778
• Email: Naureen.Starling[@]rmh.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical 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 and the subsequent recovery period.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 294
• Est. completion date: December 31, 2025
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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).

Exclusion criterion:

• Patients with an established histological diagnosis adequate to support standard of care treatment

PART 2:

Inclusion criteria

• 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

Exclusion criteria

1. Previously diagnosed invasive or haematological malignancy within the past 3 years

2. Outcome at the molecular tumour board not supportive of cancer diagnosis (possibly consistent or not consistent)

Related Conditions & MeSH terms

• Biliary Tract Neoplasms
• Colorectal Neoplasms
• Gastro Intestinal Stromal Tumour
• Gastrointestinal Stromal Tumors
• Lung Neoplasms
• Neoplasm of Lung
• Neoplasm, Bladder
• Neoplasm, Colorectal
• Neoplasms
• Neoplasms Pancreatic
• Urinary Bladder Neoplasms

Intervention

Other:
• ctDNA blood sampling
Screening/baseline blood sample to be analysed for ctDNA

Locations

Country	Name	City	State
United Kingdom	Royal Marsden Hospital	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	Throughout study completion, up to one year
Secondary	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	Throughout study completion, up to one year
Secondary	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	Throughout study completion, up to one year
Secondary	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	Throughout study completion, up to one year
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 1a	Treatment response objective response rate	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 1b	Progression free survival	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 1c	Overall survival	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 2	Proportion of patients who undergo a repeated invasive procedure	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 3a- comparison with NHS targets	Comparison of diagnostic pathway duration with NHS faster Diagnostic Standard (FDS)	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 3b- comparison with NHS targets	Comparison of diagnostic pathway duration with 62 day wait target	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 4a	Type of complications from invasive diagnostic procedures	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 4b	Frequency of complications from invasive diagnostic procedures	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 4c	Severity of complications from invasive diagnostic procedures	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 5	Number and type of invasive procedures performed	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 5b	Number of histopathology reviews	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 5c	Number of tissue based NGS performed	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 6a	Healthcare costs associated with diagnostic pathway	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 6b	Cost per-quality adjusted-life-year of diagnostic pathway	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 6c	Number of hospital visits in diagnostic pathway	To run parallel for 12 months alongside the ACCESS implementation programme
Secondary	PREVAIL ctDNA Part 2 Study secondary end point 6d	Length of hospital stay during diagnostic pathway	To run parallel for 12 months alongside the ACCESS implementation programme