Selecting Hypoxic Tumours for Treatment Modification

NCT06787053 | Recruiting

• 1 other identifier: 24_DOG13_38
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Bladder (Urothelial, Transitional Cell) Cancer; Prostate Cancer

Keywords

Hypoxia; Bladder; Cervix; Prostate; Hypoxia Modification

Outcome Measures

Primary Outcomes (1)

• Primary

  To have collected the FFPE tumour blocks and generate the gene signature.

  Through to study completion, until May 2028

Secondary Outcomes (1)

• Secondary Outcome Measure

  end of the study in May 2028

Study Arms (3)

Bladder

Patients diagnosed with bladder cancer

Prostate

Patients diagnosed with prostate cancer

Cervix

Patients diagnosed with cervical cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient recruitment will be via the disease site clinics .

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• University of Manchester: lead

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Related Publications (7)

• 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.

  PMID: 35447566 BACKGROUND

• Batis 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.

  PMID: 34192550 BACKGROUND

• Yang 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.

  PMID: 28400426 BACKGROUND

• Yang 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.

  PMID: 29729848 BACKGROUND

• Lane 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.

  PMID: 35079065 BACKGROUND

• Forker 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.

  PMID: 37085598 BACKGROUND

• Eustace 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.

  PMID: 23820108 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and formalin-fixed paraffin-embedded (FFPE) tumour biopsy

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms; Hypoxia

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ananya Choudhury, Professor

  University of Manchester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Reed, MSc

CONTACT

01619184780; rachel.reed@manchester.ac.uk

Kimberley Reeves, PhD

CONTACT

01619184780; kimberley.reeves@manchester.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: January 22, 2025
• Study Start: October 16, 2024
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

GB (1)