PAN-study: Pan-Cancer Early Detection Study (PAN)

NCT ID: NCT03756597

Last Updated: 2023-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

268 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-09-26

Study Completion Date

2023-07-06

Brief Summary

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The PAN-cancer Early Detection study or PAN-study is a prospective cross-sectional observational case-control study evaluating whether Breath Biopsy can differentiate between patients with and without different cancer types by comparing breath biomarkers for a range of cancer types including patients with gastric, oesophageal, and liver cancer.

The research may be extended to include also pancreatic, renal, prostate and bladder cancer patients, however in agreement between Cambridge University Hospital NHS Foundation Trust, University of Cambridge, CRUK and Owlstone Medical recruitment in these arms will not start until further notice. When recruitment is planned to start in these arms, Owlstone Medical will ensure to notify the REC. Subjects with a histologically confirmed cancer will be recruited from CUH by local research staff. Breath samples will be collected by means of the ReCIVA breath sampler which requires tidal breathing into a face mask for around 10 minutes. A cancer free control subject matched for age, sex and tumour specific risk factors will be recruited and sampled.

Detailed Description

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There is a pressing need for techniques that allow detection of cancer at an earlier stage when curative treatment is more likely. Exhaled biomarkers are known to reflect a wide range of metabolic processes, including those related to cancer such as the Warburg effect. Owlstone Medical Ltd (hereafter referred to as Owlstone Medical) has developed Breath Biopsy; a workflow to collect and analyse breath Volatile Organic Compounds (VOCs) in a highly standardised way. The PAN-study is a collaborative effort between Cambridge University Hospitals NHS Foundation Trust (CUH), University of Cambridge (UoC), Cancer Research United Kingdom (CRUK) and Owlstone Medical to evaluate the potential of Breath Biopsy to detect various types of cancer by profiling breath metabolites.

The PAN-cancer Early Detection study or PAN-study is a prospective cross-sectional observational case-control study evaluating whether Breath Biopsy can differentiate between patients with and without different cancer types by comparing breath biomarkers for a range of cancer types including patients with gastric, oesophageal, and liver cancer.

The research may be extended to include also pancreatic, renal, prostate and bladder cancer patients, however in agreement between Cambridge University Hospital NHS Foundation Trust, University of Cambridge, CRUK and Owlstone Medical recruitment in these arms will not start until further notice. When recruitment is planned to start in these arms, Owlstone Medical will ensure to notify the REC. Subjects with a histologically confirmed cancer will be recruited from CUH by local research staff. Breath samples will be collected by means of the ReCIVA breath sampler which requires tidal breathing into a face mask for around 10 minutes. A cancer free control subject matched for age, sex and tumour specific risk factors will be recruited and sampled. Breath samples will be shipped to Owlstone Medical for analysis of breath biomarkers by Gas Chromatography-Time Of Flight-Mass Spectrometry (GC-TOF-MS) and Gas Chromatography-Field Asymmetric Ion Mobility Spectrometry (GC-FAIMS).

This study will be the first step towards evaluating VOCs analysis as a test to improve early detection rates for cancer with future applicability to primary care. Ultimately, such a research program could enable low cost and widespread targeted screening programs for cancer.

In a subset of up to 12 patients with cirrhosis and 12 healthy volunteers, a sub study will be conducted to measure the washout of limonene after ingestion of a standardised quantity of limonene under controlled circumstance for food and drink intake.

The objective of this limonene sub-study is to demonstrate that limonene is a biomarker that differentiates between healthy individuals and cirrhotic patients with Child-Pugh grade A and B with or without HCC as a comorbidity.

Participants will be asked to visit the clinical site to provide 6 breath samples at different timepoints before and after ingestion of limonene. Participants will be asked to fast overnight for 10 hours, not to have brushed their teeth for 2 hours prior to first breath sample and not be a current smoker or should not have smoked in the past 6 months. Non-abstinent patients with alcohol related liver disease or participants who drink to excess daily will be excluded from this sub-study.

Conditions

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Gastric Cancer Esophageal Cancer Liver Cancer

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Cases Pathway A

Case pathway A - Intention to diagnose population

Only patients with a very high clinical suspicion based on imaging are scheduled for surgical procedures.Subjects with a confirmed diagnosis of cancer after clinical work-up will be labelled cases. of the study.

Patients with Gastric or Oesophageal cancer will be recruited after confirmation of their diagnosis but prior to initiation of therapy.

ReCIVA

Intervention Type DEVICE

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

CASPER

Intervention Type DEVICE

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Clinical Controls

Clinical controls represent subjects that:

* Are suspected of the same cancer or part of an at risk-group
* Have undergone full per-guideline diagnostic work-up, resulting in confirmation the subject does not have cancer (see section 6)
* Is matched to the case for age, gender and known risk-factors specific to that tumour type (section 5.4)

ReCIVA

Intervention Type DEVICE

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

CASPER

Intervention Type DEVICE

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Healthy volunteers

Healthy volunteers will be recruited from the clinical research facility at Addenbrooke's Hospital (Cambridge) or from the Cambridge BioResource. These subjects will be selected to have a similar age and sex distribution as the overall PAN-study cases.

ReCIVA

Intervention Type DEVICE

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

CASPER

Intervention Type DEVICE

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Substudy Cases

Patients with a confirmed diagnosis of cirrhosis and providing up to 6 samples will be labelled as the washout substudy cases

ReCIVA

Intervention Type DEVICE

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

CASPER

Intervention Type DEVICE

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Cases Pathway B

Case pathway B - Confirmed malignancy population

Patients with a Gastric, Liver or Oesophageal cancer will be recruited after confirmation of their diagnosis but prior to initiation of therapy. Patients will be recruited by research staff at the clinic they are referred to for diagnosis and/or treatment

ReCIVA

Intervention Type DEVICE

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

CASPER

Intervention Type DEVICE

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Interventions

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ReCIVA

The ReCIVA breath sampler contains a CO2 and pressure sensor, which allows the operator to monitor the breath sampling procedure and patient comfort. Both the operator and the patient can pause or abort the breath sampling procedure within seconds by removing the mask. The time investment required from patients is approximately 15 minutes for consenting and medical history and 10 minutes per breath collection.

Intervention Type DEVICE

CASPER

Minimizes contamination of breath samples by external VOCs Removes need for clean air supply line

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Aged 30 years or over
2. Ability to provide informed consent

Exclusion Criteria

1. (Anticipated) inability to complete the breath sampling procedure due to e.g. inability to maintain adequate ventilation unaided or claustrophobia
2. Participation in a Clinical Trial Investigational Medicinal Product (CTIMP) during the 28 days prior to breath biopsy.
3. Any biopsy or endoscopic procedure conducted during the past 48 hours. A breath sample can be collected \>48 hours post procedure.
4. Any disorder that is not stable in the opinion of the investigator. Specifically, subjects should be excluded if:

4.1. Currently in the process of investigation for a malignancy other than the tumours of interest to this study.

4.2. A history of malignancy, unless treated with curative intent and cancer-free at least 2 years prior to inclusion. Patients previously treated for highly localised disease e.g. basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that curative therapy was completed at least 12 months prior to inclusion.

4.3. A history of the malignancy the patient is currently being investigated for. E.g. a patient suspected of gastric cancer with previous gastric cancer in medical history 4.4. Known active bacterial, fungal or viral infection including but not limited to upper respiratory tract infection, tuberculosis, pneumonia, cystitis, pyelonephritis, gastritis, prostatitis or viral hepatitis. Patients can be recruited after being symptom free for at least 2 weeks for mild infections and 6 weeks if admitted to the hospital and/or treated with i.v. antibiotics.

4.5. Documented history of a clinically important lung condition other than asthma or COPD e.g., active lung infection, , bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis/mycosis, pulmonary fibrosis or hypersensitivity pneumonitis, α1- antitrypsin deficiency. If α1- antitrypsin deficiency is diagnosed after a breath sample has been taken, the patient sample may still be used for analysis. α1- antitrypsin carriers are eligible for the study.

4.6. Asthma or COPD exacerbation requiring hospitalisation and/or administration of oral prednisolone in past 6 weeks.

4.7. Renal failure stages 3b and above (eGFR 45ml/min or less) 4.8. Any hospitalisation for symptoms unrelated to the clinical presentation of the tumour under investigation during the past 6 weeks.
5. Immunocompromised patients: specifically, patients with Acquired Immune Deficiency Syndrome (AIDS) (HIV with normal blood counts is eligible), inborn or acquired severe immune-deficiency including those caused by pharmacological treatment.
6. Documented history of pulmonary surgery or endobronchial interventional procedures other than biopsy, lavage or bronchial brushings. These include surgical resection, VATS, bronchial thermoplasty and coiling.
7. Applicable for the limonene sub-study only (see section 4.1): Non-abstinent participants with alcohol related liver disease or participants who drink to excess daily.
8. Applicable for the limonene sub-study only (see section 4.1): Current smokers (or e-cigarette users) or participants who have smoked (or used e-cigarettes) in the past 6 months prior to baseline sample.
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cancer Research UK

OTHER

Sponsor Role collaborator

Owlstone Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marc P van der Schee, MD, PhD

Role: STUDY_DIRECTOR

+01223 428200

Prof Rebecca Fitzgerald, MD, PhD

Role: STUDY_CHAIR

Cambridge University Hospital

Massimiliano di Pietro, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Mr Vincent J Gnanapragasam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Mr Grant Stewart, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Dr Godfrey Edmund, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Miss Alexandra Colquhoun,

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Dr Victoria Snowdon

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Dr Matthew Hoare

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Dr Michael Allison

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospital

Locations

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Cambridge University Hospital NHS

Cambridge, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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Other Identifiers

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PAN

Identifier Type: -

Identifier Source: org_study_id

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