Bladder (Urothelial, Transitional Cell) CancerSELECTNCT06787053
Selecting Hypoxic Tumours for Treatment Modification
An observational study of Bladder (Urothelial, Transitional Cell) Cancer and Prostate Cancer, run by University of Manchester at 1 site in United Kingdom.
Trial summary
Approximately 50% of cancer patients with solid tumours will be treated with radiotherapy. A significant proportion (>25%) of patients have hypoxic tumours which respond poorly to radiotherapy. Hypoxic tumours have a poor prognosis. This can be improved with treatment intensification. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder (Urothelial, Transitional Cell) Cancer, Prostate Cancer
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Oct 2024to 30 May 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient recruitment will be via the disease site clinics .
Who may be able to join
- This will be tumour site dependent.
- Bladder:
- Older than age 18 years.
- Patients having radiotherapy at the Christie NHS Foundation Trust suitable for imaging on an MRI scanner.
- Able to give informed consent.
- Cervix:
Show all 13Show fewer
- Older than age 18 years.
- Patients having radiotherapy at the Christie NHS Foundation Trust suitable for imaging on an MRI scanner.
- Able to give informed consent.
- Prostate:
- Older than age 18 years.
- Patients having radiotherapy at the Christie NHS Foundation Trust suitable for imaging on an MRI scanner.
- Able to give informed consent.
Who cannot join
- This will be tumour site dependent
- Bladder:
- Any contraindications to MRI identified after MRI safety screening including completion of an MRI Safety Screening Form.
- Unable to tolerate MRI scans.
- Pregnancy.
- Cervix:
Show all 12Show fewer
- Any contraindications to MRI identified after MRI safety screening including completion of an MRI Safety Screening Form.
- Unable to tolerate MRI scans.
- Pregnancy.
- Prostate:
- Any contraindications to MRI identified after MRI safety screening including completion of an MRI Safety Screening Form.
- Unable to tolerate MRI scans
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
The Christie NHS Foundation Trust
Manchester
Rachel Reed, MSc, 01619187480 ext. 7480, rachel.reed@manchester.ac.uk
Kimberley Reeves, PhD, 01619187480 ext. 7480, kimberley.reeves@manchester.ac.uk
About this study
Approximately 50% of cancer patients with solid tumours will be treated with radiotherapy. A significant proportion (>25%) of patients have hypoxic tumours which respond poorly to radiotherapy. Hypoxic tumours have a poor prognosis. This can be improved with treatment intensification. Treatment intensification can be modification with CON (breathing O2-enriched air + oral administration of nicotinamide), chemoradiosensitisation, radiation dose-escalation or additional systemic treatments, significantly improving response of the tumours to radiotherapy. However, there are currently no clinically approved biomarkers to identify hypoxic tumours. Our group has developed and validated gene-expression signature-based biomarkers that identify patients with hypoxic bladder, head and neck , prostate, sarcoma and lung cancers. The bladder cancer gene-expression hypoxia signature has been shown to predict benefit from hypoxia modification using RNA from archived tumour tissue. The main purpose of this study is to demonstrate in at least two cancer types that the hypoxia biomarker predicts benefit from hypoxia modification in real-time.
Read the detailed description
Research Question: Can hypoxia biomarkers personalised treatment improve cancer outcomes?
Cancers that are hypoxic (have a high percentage of regions of low local O2 concentration) are refractory to radiotherapy but benefit from hypoxia modification. However, there are no biomarkers to identify patients with hypoxic tumours. The gold standard for determining tissue O2 concentration is the O2-electrode which takes measurements at several sites within the tumour. However, this necessitates insertion of a needle into multiple regions of the tumour so is invasive and provides only a localised hypoxia status. Other hypoxia biomarkers that identify hypoxia have been derived from cell surface protein expression, gene expression or imaging outputs. Proteins expressed on the tumour cell surface of hypoxic cells include CA9 and glut1 but the expression of these proteins is not specific to hypoxia and is highly heterogeneous within tumours. Whilst expression of HIF1 by hypoxic tumours has been shown not to predict benefit from hypoxia-modification. Gene signatures are a set of genes in which the collective changed expression has been validated to demonstrate diagnosis, prognosis or predict therapeutic response. Gene expression is consistently altered across tumours with high hypoxic fractions meaning that they are robust indicators of hypoxia status.
Using RNA extracted from archived material (Formalin fixed paraffin embedded tumour tissue) our gene-expression signature-based biomarkers for bladder, head and neck, prostate, sarcoma, cervical and lung cancers have been validated by demonstrated prognosis in each of the cancer groups. Further the 24 gene bladder cancer hypoxia signature has been shown to be predictive of benefit from hypoxia modification for patients with hypoxic tumours receiving radiotherapy. A recent review of predictive biomarkers in cancer treatment has shown that this is the only predictive biomarker for hypoxia-modification during radiotherapy.
Hypoxic regions in tumours can also be identified using MRI techniques including O2-senstive MRI (OE-MRI) and Intravoxel incoherent motion imaging. Combining imaging with gene expression data results in more accurate assessment of hypoxic status and identify tumour subtype which further contributes to personalised clinical decisions. MRI-based techniques also facilitate localized personalization approaches, e.g., for hypoxia-directed focal radiotherapy dose escalation.
Primary Question/Objective:
Short objective; to establish trials to test if personalised use of established hypoxia-targeted treatments with radiotherapy improves survival and work with the North West Genomics Hub to progress implementing our tissue hypoxia test for delivery across the NHS.
Medium objective; integrate MR imaging in the workflow for measuring hypoxia in at least two tumour sites.
Secondary Question/Objective:
- Integrate radiological parameters with the hypoxia biomarker for personalising treatment.
- Can blood-based biomarkers be early response biomarkers.
- Keywords
- Hypoxia, Bladder, Cervix, Prostate, Hypoxia Modification
- Medical subject headings
- Neoplasms, Prostatic Neoplasms, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Bladder | Patients diagnosed with bladder cancer | |
| Prostate | Patients diagnosed with prostate cancer | |
| Cervix | Patients diagnosed with cervical cancer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary
To have collected the FFPE tumour blocks and generate the gene signature.
Measured: Through to study completion, until May 2028
Secondary outcomes (1)
Secondary Outcome Measure
To have collected a total of at least 4 different patient blood samples which have corresponding MRI scans from each participant in this study undergoing imaging or treatment.
To have developed and optimised MR sequences, which can be used across Manchester and Lancashire in at least two tumour sites.
Measured: end of the study in May 2028
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2025
- Study start16 Oct 2024
- Primary completion30 May 2028 (estimated)
- Study completion30 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Bladder (Urothelial, Transitional Cell) CancerStudies of the same condition, open and under way.
- More trials run by University of ManchesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ananya Choudhury, University of Manchester
- Investigators
- Ananya Choudhury, Professor, Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06787053
- Sponsor's protocol ID
- 24_DOG13_38
- Acronym
- SELECT
- Status last verified
- May 2026
- First submitted
- 13 Dec 2024
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Swartz JE, Smits HJG, Philippens MEP, de Bree R, H A M Kaanders J, Willems SM. Correlation and colocalization of HIF-1alpha and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas: A digital, single-cell-based analysis. Oral Oncol. 2022 May;128:105862. doi: 10.1016/j.oraloncology.2022.105862. Epub 2022 Apr 18.
PubMed 35447566Batis N, Brooks JM, Payne K, Sharma N, Nankivell P, Mehanna H. Lack of predictive tools for conventional and targeted cancer therapy: Barriers to biomarker development and clinical translation. Adv Drug Deliv Rev. 2021 Sep;176:113854. doi: 10.1016/j.addr.2021.113854. Epub 2021 Jun 27.
PubMed 34192550Yang L, Taylor J, Eustace A, Irlam JJ, Denley H, Hoskin PJ, Alsner J, Buffa FM, Harris AL, Choudhury A, West CML. A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients. Clin Cancer Res. 2017 Aug 15;23(16):4761-4768. doi: 10.1158/1078-0432.CCR-17-0038. Epub 2017 Apr 11.
PubMed 28400426Yang L, Roberts D, Takhar M, Erho N, Bibby BAS, Thiruthaneeswaran N, Bhandari V, Cheng WC, Haider S, McCorry AMB, McArt D, Jain S, Alshalalfa M, Ross A, Schaffer E, Den RB, Jeffrey Karnes R, Klein E, Hoskin PJ, Freedland SJ, Lamb AD, Neal DE, Buffa FM, Bristow RG, Boutros PC, Davicioni E, Choudhury A, West CML. Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer. EBioMedicine. 2018 May;31:182-189. doi: 10.1016/j.ebiom.2018.04.019. Epub 2018 Apr 23.
PubMed 29729848Lane B, Khan MT, Choudhury A, Salem A, West CML. Development and validation of a hypoxia-associated signature for lung adenocarcinoma. Sci Rep. 2022 Jan 25;12(1):1290. doi: 10.1038/s41598-022-05385-7.
PubMed 35079065Forker LJ, Bibby B, Yang L, Lane B, Irlam J, Mistry H, Khan M, Valentine H, Wylie J, Shenjere P, Leahy M, Gaunt P, Billingham L, Seddon BM, Grimer R, Robinson M, Choudhury A, West C. Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma. Br J Cancer. 2023 Jun;128(12):2307-2317. doi: 10.1038/s41416-023-02265-3. Epub 2023 Apr 21.
PubMed 37085598Eustace A, Mani N, Span PN, Irlam JJ, Taylor J, Betts GN, Denley H, Miller CJ, Homer JJ, Rojas AM, Hoskin PJ, Buffa FM, Harris AL, Kaanders JH, West CM. A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer. Clin Cancer Res. 2013 Sep 1;19(17):4879-88. doi: 10.1158/1078-0432.CCR-13-0542. Epub 2013 Jul 2.
PubMed 23820108
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selecting Hypoxic Tumours for Treatment Modification
- ClinicalTrials.gov ID
- NCT06787053
- Acronym / sponsor ID
- SELECT / 24_DOG13_38
- Keywords
- Hypoxia, Bladder, Cervix, Prostate, Hypoxia Modification
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Study start
- 16 Oct 2024 (actual)
- Primary completion
- 30 May 2028 (estimated)
- Study completion
- 30 May 2028 (estimated)
- First posted
- 22 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 50% of cancer patients with solid tumours will be treated with radiotherapy. A significant proportion (>25%) of patients have hypoxic tumours which respond poorly to radiotherapy. Hypoxic tumours have a poor prognosis. This can be improved with treatment intensification. Treatment intensification can be modification with CON (breathing O2-enriched air + oral administration of nicotinamide), chemoradiosensitisation, radiation dose-escalation or additional systemic treatments, significantly improving response of the tumours to radiotherapy. However, there are currently no clinically approved biomarkers to identify hypoxic tumours. Our group has developed and validated gene-expression signature-based biomarkers that identify patients with hypoxic bladder, head and neck , prostate, sarcoma and lung cancers. The bladder cancer gene-expression hypoxia signature has been shown to predict benefit from hypoxia modification using RNA from archived tumour tissue. The main purpose of this study is to demonstrate in at least two cancer types that the hypoxia biomarker predicts benefit from hypoxia modification in real-time.
Detailed description
Research Question: Can hypoxia biomarkers personalised treatment improve cancer outcomes?
Cancers that are hypoxic (have a high percentage of regions of low local O2 concentration) are refractory to radiotherapy but benefit from hypoxia modification. However, there are no biomarkers to identify patients with hypoxic tumours. The gold standard for determining tissue O2 concentration is the O2-electrode which takes measurements at several sites within the tumour. However, this necessitates insertion of a needle into multiple regions of the tumour so is invasive and provides only a localised hypoxia status. Other hypoxia biomarkers that identify hypoxia have been derived from cell surface protein expression, gene expression or imaging outputs. Proteins expressed on the tumour cell surface of hypoxic cells include CA9 and glut1 but the expression of these proteins is not specific to hypoxia and is highly heterogeneous within tumours. Whilst expression of HIF1 by hypoxic tumours has been shown not to predict benefit from hypoxia-modification. Gene signatures are a set of genes in which the collective changed expression has been validated to demonstrate diagnosis, prognosis or predict therapeutic response. Gene expression is consistently altered across tumours with high hypoxic fractions meaning that they are robust indicators of hypoxia status.
Using RNA extracted from archived material (Formalin fixed paraffin embedded tumour tissue) our gene-expression signature-based biomarkers for bladder, head and neck, prostate, sarcoma, cervical and lung cancers have been validated by demonstrated prognosis in each of the cancer groups. Further the 24 gene bladder cancer hypoxia signature has been shown to be predictive of benefit from hypoxia modification for patients with hypoxic tumours receiving radiotherapy. A recent review of predictive biomarkers in cancer treatment has shown that this is the only predictive biomarker for hypoxia-modification during radiotherapy.
Hypoxic regions in tumours can also be identified using MRI techniques including O2-senstive MRI (OE-MRI) and Intravoxel incoherent motion imaging. Combining imaging with gene expression data results in more accurate assessment of hypoxic status and identify tumour subtype which further contributes to personalised clinical decisions. MRI-based techniques also facilitate localized personalization approaches, e.g., for hypoxia-directed focal radiotherapy dose escalation.
Primary Question/Objective:
Short objective; to establish trials to test if personalised use of established hypoxia-targeted treatments with radiotherapy improves survival and work with the North West Genomics Hub to progress implementing our tissue hypoxia test for delivery across the NHS.
Medium objective; integrate MR imaging in the workflow for measuring hypoxia in at least two tumour sites.
Secondary Question/Objective:
- Integrate radiological parameters with the hypoxia biomarker for personalising treatment.
- Can blood-based biomarkers be early response biomarkers.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bladder | – | –Patients diagnosed with bladder cancer |
| Prostate | – | –Patients diagnosed with prostate cancer |
| Cervix | – | –Patients diagnosed with cervical cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient recruitment will be via the disease site clinics .
Key inclusion criteria (13 listed)
- This will be tumour site dependent.
- Older than age 18 years.
- Patients having radiotherapy at the Christie NHS Foundation Trust suitable for imaging on an MRI scanner.
- Able to give informed consent.
- Older than age 18 years.
Key exclusion criteria (12 listed)
- This will be tumour site dependent
- Any contraindications to MRI identified after MRI safety screening including completion of an MRI Safety Screening Form.
- Unable to tolerate MRI scans.
- Pregnancy.
- Any contraindications to MRI identified after MRI safety screening including completion of an MRI Safety Screening Form.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Primary
Time frame: Through to study completion, until May 2028
To have collected the FFPE tumour blocks and generate the gene signature.
1 secondary outcome
Secondary Outcome Measure
Time frame: end of the study in May 2028
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Background: PubMed 35447566Swartz JE, Smits HJG, Philippens MEP, de Bree R, H A M Kaanders J, Willems SM. Correlation and colocalization of HIF-1alpha and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas: A digital, single-cell-based analysis. Oral Oncol. 2022 May;128:105862. doi: 10.1016/j.oraloncology.2022.105862. Epub 2022 Apr 18.
- Background: PubMed 34192550Batis N, Brooks JM, Payne K, Sharma N, Nankivell P, Mehanna H. Lack of predictive tools for conventional and targeted cancer therapy: Barriers to biomarker development and clinical translation. Adv Drug Deliv Rev. 2021 Sep;176:113854. doi: 10.1016/j.addr.2021.113854. Epub 2021 Jun 27.
- Background: PubMed 28400426Yang L, Taylor J, Eustace A, Irlam JJ, Denley H, Hoskin PJ, Alsner J, Buffa FM, Harris AL, Choudhury A, West CML. A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients. Clin Cancer Res. 2017 Aug 15;23(16):4761-4768. doi: 10.1158/1078-0432.CCR-17-0038. Epub 2017 Apr 11.
- Background: PubMed 29729848Yang L, Roberts D, Takhar M, Erho N, Bibby BAS, Thiruthaneeswaran N, Bhandari V, Cheng WC, Haider S, McCorry AMB, McArt D, Jain S, Alshalalfa M, Ross A, Schaffer E, Den RB, Jeffrey Karnes R, Klein E, Hoskin PJ, Freedland SJ, Lamb AD, Neal DE, Buffa FM, Bristow RG, Boutros PC, Davicioni E, Choudhury A, West CML. Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer. EBioMedicine. 2018 May;31:182-189. doi: 10.1016/j.ebiom.2018.04.019. Epub 2018 Apr 23.
- Background: PubMed 35079065Lane B, Khan MT, Choudhury A, Salem A, West CML. Development and validation of a hypoxia-associated signature for lung adenocarcinoma. Sci Rep. 2022 Jan 25;12(1):1290. doi: 10.1038/s41598-022-05385-7.
- Background: PubMed 37085598Forker LJ, Bibby B, Yang L, Lane B, Irlam J, Mistry H, Khan M, Valentine H, Wylie J, Shenjere P, Leahy M, Gaunt P, Billingham L, Seddon BM, Grimer R, Robinson M, Choudhury A, West C. Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma. Br J Cancer. 2023 Jun;128(12):2307-2317. doi: 10.1038/s41416-023-02265-3. Epub 2023 Apr 21.
- Background: PubMed 23820108Eustace A, Mani N, Span PN, Irlam JJ, Taylor J, Betts GN, Denley H, Miller CJ, Homer JJ, Rojas AM, Hoskin PJ, Buffa FM, Harris AL, Kaanders JH, West CM. A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer. Clin Cancer Res. 2013 Sep 1;19(17):4879-88. doi: 10.1158/1078-0432.CCR-13-0542. Epub 2013 Jul 2.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ananya Choudhury, Professor principal investigator
University of Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder (Urothelial, Transitional Cell) Cancer and Prostate Cancer, run by University of Manchester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachel Reed, MSc (01619184780 ext. 7480, rachel.reed@manchester.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary (time frame: Through to study completion, until May 2028). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06787053, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.