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

NCT03756597 | Completed

• 1 other identifier: PAN
• Study Type: observational
• Target: 268
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer; Esophageal Cancer; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Primary endpoints; accuracy of breath biopsy to discriminate between individuals with and without cancer

  o These will include gastric, oesophageal and liver and matched controls. This analysis will be conducted by combining cases and matched controls across all cancer types as well as when stratified per tumour type. If supported by literature on the presence of potential biomarkers related to pancreatic, renal, prostate, and bladder tumours similar analysis will be done in samples collected in patients diagnosed with these cancer types and controls.

  3 years

Secondary Outcomes (1)

• Patient feedback on usability and acceptability of Breath Biopsy as assessed using a a structured interview

  3 years

Other Outcomes (1)

• Exploratory endpoints; influence of tumour phenotype on breath VOCs:

  3 years

Study Arms (5)

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.

Device: ReCIVA; Device: CASPER

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)

Device: ReCIVA; Device: CASPER

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.

Device: ReCIVA; Device: CASPER

Substudy Cases

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

Device: ReCIVA; Device: CASPER

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

Device: ReCIVA; Device: CASPER

Interventions

ReCIVA 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.

Cases Pathway A; Cases Pathway B; Clinical Controls; Healthy volunteers; Substudy Cases

CASPER DEVICE

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

Cases Pathway A; Cases Pathway B; Clinical Controls; Healthy volunteers; Substudy Cases

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The inclusion and exclusion criteria for the various study populations are detailed above. General inclusion and exclusion criteria which apply to all study subjects are detailed followed by indication specific criteria are also detailed for both inclusion and exclusion.

You may qualify if:

• Aged 30 years or over
• Ability to provide informed consent

You may not qualify if:

• (Anticipated) inability to complete the breath sampling procedure due to e.g. inability to maintain adequate ventilation unaided or claustrophobia
• Participation in a Clinical Trial Investigational Medicinal Product (CTIMP) during the 28 days prior to breath biopsy.
• Any biopsy or endoscopic procedure conducted during the past 48 hours. A breath sample can be collected \>48 hours post procedure.
• Any disorder that is not stable in the opinion of the investigator. Specifically, subjects should be excluded if:
• Currently in the process of investigation for a malignancy other than the tumours of interest to this study.
• 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.
• 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.
• Asthma or COPD exacerbation requiring hospitalisation and/or administration of oral prednisolone in past 6 weeks.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Owlstone Ltd: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Cancer Research UK: collaborator

Study Sites (1)

Cambridge University Hospital NHS

Cambridge, CB2 0QQ, United Kingdom

Location

Related Links

• PAN study website

Biospecimen

Retention: SAMPLES WITHOUT DNA

Patients will inhale room air from which environmental VOCs have been removed to prevent contamination of the sample. The mask contains a CO2 sensor that drives two micro-pumps in the mask that sample alveolar and bronchial breath separately. This is relevant because different cancer biomarkers can be found in different portions of breath. During the procedure the breath will automatically be sampled onto four sorbent tubes to collect a total of 1.5L of breath. The procedure will normally take around 10 minutes, very rarely exceeding 15 minutes if exhaled volumes are small. After collection, the sorbent tubes are stored in the refrigerator at 4-8°C until shipment to Owlstone Medical. For those participating in the washout sub study, up to 6 samples will be obtained at various timepoints in one day.

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Liver Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Liver Diseases

Study Officials

• Marc P van der Schee, MD, PhD

  +01223 428200

  STUDY DIRECTOR

• Prof Rebecca Fitzgerald, MD, PhD

  Cambridge University Hospital

  STUDY CHAIR

• Massimiliano di Pietro, MD, PhD

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Mr Vincent J Gnanapragasam, MD, PhD

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Mr Grant Stewart, MD, PhD

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Dr Godfrey Edmund, MD, PhD

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Miss Alexandra Colquhoun,

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Dr Victoria Snowdon

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Dr Matthew Hoare

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

• Dr Michael Allison

  Cambridge University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: November 28, 2018
• Study Start: September 26, 2018
• Primary Completion: December 2, 2022
• Study Completion: July 6, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-10

Locations

GB (1)