NCT05702619

Hypoxia-driven Prostate Cancer Genomics (HYPROGEN)

Hypoxia-driven Prostate Cancer Genomics (HYPROGEN) - Illuminating the Genomic Landscape of Hypoxia-driven Early Metastatic Prostate Cancer

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 60 (estimated)
• Sponsor: The Christie NHS Foundation Trust · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Due to the rapid growth, tumour demand for oxygen is often higher than what can be delivered by the newly forming blood vessels. Tumour adaption to this imbalanced oxygen supply and demand (hypoxia) is associated with poor prognosis and genetic changes (genomic instability) that allow it to become more resistant to chemo- and radiotherapy. Patients with hypoxic tumours therefore die earlier. Limited information is available on hypoxia in newly diagnosed prostate cancer, especially to what degree hypoxia in the prostate tumour is associated with the presence of metastases to bones. The Hyprogen trial is a prospective, non-randomised, exploratory biopsy and imaging biomarker study recruiting 60 patients with prostate cancer to better establish the role of hypoxia in prostate cancer cells evolution and early metastatic spread.

Detailed description

Arm 1 of this study will aim to determine the association between hypoxia in the primary tumour with the presence of skeletal metastases and aim to determine if hypoxia is also present in the metastatic sites themselves. Arm 2 will aim to determine the genetic changes associated with hypoxia in cancers that have not spread outside the prostate. Hypoxia presence will be determined by using a hypoxia identifying stain (by giving a patient a tablet of the stain to take orally) and by identifying genomic alterations that are associated with hypoxia. After taking the tablet of the hypoxia marker (Pimonidazole) patients in Arm 1 will receive both a biopsy of the prostate and of one or two of the bone metastases. The presence or not as well as the degree of hypoxia in both sites will be assessed. Patients in Arm 2 will receive pimonidazole prior to a planned radical prostatectomy and the heterogeneity of hypoxia related genetic change throughout the prostate will assessed. Arm 2 patients will undergo MRI hypoxia imaging to validate the detection of pimonidazole marked hypoxic regions with a non-invasive imaging method.

Conditions

• Prostate Cancer
• Hypoxia

Interventions

Type	Name	Description
DRUG	Optional non-IMP pimonidazole	patients will be asked to ingest an oral formulation of pimonidazole hydrochloride (HCl) (Oral HypoxyprobeTM-1). Pimonidazole HCl is a marker for hypoxia in tumour tissue when ingested as an encapsulated solid. Following oral administration, pimonidazole distributes throughout the body where it covalently binds to normal and tumour tissues that have regions of low oxygen concentrations (pO2 of ≤ 10 mmHg at 37oC). The tissue binding can be visualised by immunohistochemistry / light microscopy. The capsules are to be taken within 8-16 hours (optimal timepoint 12 hours) before the planned first biopsy within Arm 1 and before radical prostatectomy for patients in Arm 2. If the patient refuses the pimonidazole, forgets to take it, or if it is not available, the patient can still participate in the study and their samples will be stained for hypoxia post-biopsy.
DIAGNOSTIC_TEST	CT-guided Bone Biopsy	A CT-guided biopsy of a bone metastasis that is deemed to be easy to biopsy and in an area without major risk for pathological fracture or bleeding will be taken during the biopsy visit. Patients will receive routine local anaesthetic of the region to be biopsied followed by thorough disinfection of the biopsy site with antiseptic wipes. Patients will be asked to fast on the day of the procedure and to have an intravenous cannula inserted to allow the use of medication causing minimal sedation (for example midazolam and/or fentanyl) during the procedure if required to alleviate discomfort or pain.
DIAGNOSTIC_TEST	TRUS-guided Targeted Transperineal Prostate Biopsy	Transperineal Prostate Biopsy will be performed following standard clinical practice of local department. This will include pre-operative oral analgesia and prophylactic antibiotic treatment according to local hospital policy for transperineal prostate biopsies.
PROCEDURE	Radical Prostatectomy	Radical Prostatectomy will be performed according to standard of care robotic approach and as relayed to the patient by the attending urologic surgeon. The side effects of the surgery are the ones reported in the literature and the latest participant information leaflet provided prior patient consent (e.g. risk of erection disfunction, incontinence, etc.).
DIAGNOSTIC_TEST	Whole-body MRI	Whole-body MR imaging (wbMRI) will be performed once, before or after the biopsy study visit, depending on available examination slots in the Department of Radiology. WbMRI images will allow comparison of the numbers of bone metastases detected by routine bone scan and wbMRI for sensitivity assessment of both techniques for oligometastatic disease.
DIAGNOSTIC_TEST	Prostate MRI scans	Patients within Arm 2 will be offered the option to undergo additional MR imaging of the pelvis in addition to any standard of care imaging acquired. In patients who agree to undergo additional scans, MRI scans will be performed on 2 occasions prior to the radical prostatectomy. MRI scans will be acquired on either the MR sim diagnostic scanner, on the MR Linac scanner or on both.
OTHER	Baseline bloods - for germline testing	Arm 1 - * 1-2 x 3.5mL blood samples collected into EDTA tubes for germ line DNA extraction and processing to PBMC for banking and future profiling of immune cell populations * 1 x 10mL serum tubes for future, biobank related research projects, ie lipidomics, metabolics and microRNA analysis ARM 2 - A blood sample (maximum 20ml) will be taken for standard of care blood tests prior to prostatectomy including Full Blood Count, Renal Function and PSA. At the same time these standard of care bloods are taken, additional bloods - a maximum of 30ml - will be taken for research purposes as required for the following downstream analysis: * Germ line DNA extraction and optional processing to PBMC for banking and future profiling of immune cell populations * Biobank related research projects, ie lipidomics, metabolics and microRNA analysis
OTHER	Baseline bloods for CTCs and ct DNA taken at same time as baseline bloods in Arm 1	2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.
OTHER	Post-pimonidazole bloods for CTCs and ctDNA	ARM 1 - 2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.

Timeline

• Start date: 2021-10-03
• Primary completion: 2023-06-30
• Completion: 2023-06-30
• First posted: 2023-01-27
• Last updated: 2023-01-27

Locations

1 site across 1 country: United Kingdom