Detection of hypoxia (low oxygen) in lung cancer using imaging
| ISRCTN | ISRCTN18092347 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18092347 |
| IRAS number | 200248 |
- Submission date
- 29/03/2018
- Registration date
- 07/08/2018
- Last edited
- 17/12/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Researchers are trying to develop good methods to detect tumour cells that are hypoxic (contain low oxygen levels), as they are less likely to be killed by anti-cancer drugs or radiotherapy. We think that PET scans may be a reliable non-invasive method of obtaining this information. This study aims to investigate two types of special scan, called FAZA-PET and FMISO-PET, that could be used to detect low oxygen levels.
Who can participate?
Participants will include any lung cancer patient in NHS Grampian who is of good fitness and being considered for surgery or radiotherapy for the treatment of their lung cancer. Patients must have a biopsy (lung tissue sample) confirming the type of lung cancer. Patients must be over 18 and can be either male or female.
What does the study involve?
The study involves patients undergoing two PET/CT scans prior to their planned treatment for lung cancer. The scans will enable us to assess the oxygen levels in patients’ tumours. The scans will be separated by a short period of 2 to 7 days. This will allow us to check how reliable the PET/CT scan test is by comparing the two scans with each other to see if they provide the same information.
What are the possible benefits and risks of participating?
There will be no immediate benefit to the patients participating but it will hopefully benefit lung cancer patients in the future. Patients will be required to spend two additional half days at the hospital for the scans to take place. There are no anticipated side effects from the scans.
Where is the study run from?
Aberdeen Royal Infirmary, NHS Grampian
When is the study starting and how long is it expected to run for?
The study will start from May 2018 and recruit for approximately 1 year until 20 patients have been recruited.
Who is funding the study?
The study is funded by Friends of ANCHOR, who have kindly funded the PET/scan costs for each patient.
Who is the main contact?
Dr Kirsten Laws, email kirstenlaws@nhs.net
Contact information
Public
Institute of Medical Sciences, University of Aberdeen, Foresterhill
Aberdeen
Ab24 2ZN
United Kingdom
Scientific
Institute of Medical Sciences, University of Aberdeen, Foresterhill
Aberdeen
Ab24 2ZN
United Kingdom
Study information
| Study design | This is an observational study that will recruit 20 patients in total who will undergo a test-retest programme to ascertain if FAZA and FMISO hypoxia PET/CT scans are reproducible with time as the only variable. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | ISRCTN18092347_PIS_v3_03Mar2018.pdf |
| Scientific title | Detection of hypoxia in non small cell lung carcinoma with [18F]FAZA-PET and [18F]FMISO-PET |
| Study objectives | The aim of this study is to use [18F]FAZA-PET and [18F]FMISO-PET to investigate whether non small cell lung carcinomas (NSCLC) may contain hypoxic regions and to compare reliability and reproducibility of the images produced by [18F]FAZA -PET and [18F]FMISO-PET retention in lung cancers when the only variable is time. THe study will also assess and develop the optimum imaging protocol for [18F]FAZA and [18F]FMISO in NSCLC and compare the reliability of the image produced by [18F]FAZA-PET and [18F]FMISO-PET with immunohistochemistry staining of tumour slices with intrinsic biomarkers of hypoxia (hypoxia-inducible factor 1α ;HIF1α) and carbonic anhydrase IX; CAIX) |
| Ethics approval(s) | North of Scotland Research Ethics Committee, October 2016,16/NS/0085 |
| Health condition(s) or problem(s) studied | Non-small cell lung cancer |
| Intervention | The study will recruit 20 patients in total. The first 10 patients will undergo a test-retest with [18F]FAZA PET, with an initial [18F]FAZA scan, followed by a subsequent [18F]FAZA scan at an interval of 2-7 days. A second set of 10 patients will undergo the same process with [18F]FMISO PET, with an initial [18F]FMISO PET followed by a subsequent [18F]FMISO PET at an interval of 2-7 days. Tumour tissue will be collected as soon as practical after the second PET scan (within 2 days of the second scan). Three additional laboratory tests will be performed on the sample obtained from the patient’s planned surgical procedure or biopsy. No additional surgical samples will be required other than the standard of care. The additional tests to be performed are however not standard of care and are being performed specifically for the biomarker part of the study. The tissue samples will be assessed by immunohistochemistry analysis of the expression of HIF1alpha and CAIX (Carbonic Anhydrase IX), and Ki67, which are well established intrinsic biomarkers of hypoxia and proliferation. These samples will provide additional information about the tumour and be compared to the results of the PET/CT scans. |
| Intervention type | Other |
| Primary outcome measure | The primary outcome measure will be to assess the reproducibility of the hypoxia PET/CT images with time as the only variable. Several metrics will be used to assess uptake, including Standardised Uptake Values (SUV), Tumour to Blood ratio (TBR) and Fractional Hypoxic volume (FHV). Reproducibility will be assessed by correlation between the values obtained for the two scans performed in each patient and an assessment of the voxel distribution and spatial correlation between the two scans will also be performed. |
| Secondary outcome measures | 1. Correlation of SUV, TBR and FHV calculated by imaging with intrinsic hypoxia biomarkers by immunohistochemistry analysis of HIF1alpha and CAIX (Carbonic Anhydrase IX), expressed as a percentage and correlation performed with the metrics for uptake values for each scan. 2. Comparison of FAZA and FMISO images and reproducibility will be assessed by comparison of the degree of reproducibility as assessed by the above measures in the primary outcome 3. Optimisation of FAZA and FMISO imaging protocols will be performed during the clinical trial by assessment of the various uptake values and imaging parameters and the information obtained at each time point (dynamic and static) of the imaging protocol 4. Overall survival (months) will be obtained for each patient in order that an assessment can be made of the correlation between tracer uptake, as measured above, and overall survival in months |
| Overall study start date | 01/06/2016 |
| Completion date | 01/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 20 |
| Key inclusion criteria | 1. Histopathological confirmation of a diagnosis of non small cell lung cancer 2. Reasonable performance status (WHO performance status 0-1) 3. Medically fit and eligible for curative surgical resection or radical chemoradiotherapy 4. Able to give informed consent |
| Key exclusion criteria | 1. Diagnosis of small cell lung cancer (SCLC) 2. WHO performance status of ≥2 3. Pregnant 4. Required to start treatment as an emergency (within 7 days) 5. Not suitable for surgical resection or radical chemoradiotherapy |
| Date of first enrolment | 26/03/2018 |
| Date of final enrolment | 01/12/2025 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Aberdeen
Ab42 2ZN
United Kingdom
Sponsor information
Other
Research Governance, Foresterhill House Annexe, Foresterhill
Aberdeen
AB25 2ZB
United Kingdom
"ROR" |
https://ror.org/00ma0mg56 |
|---|
Funders
Funder type
Not defined
No information available
No information available
No information available
Results and Publications
| Intention to publish date | 01/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | The intention is to fully publish the results of this trial in a scientific journal on completion of the study. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository within Aberdeen Royal Infirmary, NHS Grampian. The data will be shared via means of presentation within a scientific paper, with all patient details fully anonymised. The data shared will include outcome measures of scans, degree of hypoxia identified, correlation between scans and immunohistochemistry results. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v3 | 03/03/2018 | 07/08/2018 | No | Yes |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN18092347_PIS_v3_03Mar2018.pdf
- Uploaded 07/08/2018
Editorial Notes
17/12/2024: The following changes were made to the trial record:
1. The overall end date was changed from 01/08/2020 to 01/12/2025.
2. The recruitment end date was changed from 26/03/2019 to 01/12/2025.
3. The study was closed due to the covid pandemic and has recently been reopened to complete recruitment.
07/08/2018: The participant information sheet has been uploaded.
