- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05702619
Hypoxia-driven Prostate Cancer Genomics (HYPROGEN) (HYPROGEN)
Hypoxia-driven Prostate Cancer Genomics (HYPROGEN) - Illuminating the Genomic Landscape of Hypoxia-driven Early Metastatic Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Optional non-IMP pimonidazole
- Diagnostic test: CT-guided Bone Biopsy
- Diagnostic test: TRUS-guided Targeted Transperineal Prostate Biopsy
- Diagnostic test: Whole-body MRI
- Other: Baseline bloods - for germline testing
- Other: Baseline bloods for CTCs and ct DNA taken at same time as baseline bloods in Arm 1
- Other: Post-pimonidazole bloods for CTCs and ctDNA
- Procedure: Radical Prostatectomy
- Diagnostic test: Prostate MRI scans
Detailed Description
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Martin Swinton
- Phone Number: 07896026629
- Email: m.swinton@nhs.net
Study Contact Backup
- Name: Fizzah M Ali
- Email: fizzah.ali@manchester.ac.uk
Study Locations
-
-
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Manchester, United Kingdom
- Recruiting
- The Christie NHS Foundation Trust
-
Contact:
- Fizzah M Ali
- Email: fizzah.ali@manchester.ac.uk
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Contact:
- Martin Swinton
- Email: m.swinton@nhs.net
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
ARM 1
Inclusion Criteria:
- Male patients aged 18 years and older
- Histologically proven adenocarcinoma of the prostate (≥cT2) or Highly suspected metastatic prostate cancer
- PSA value of ≥ 20 ng/mL
Multiple lesions (≥ 5) suspicious of metastatic spread on routine imaging procedures with at least one amenable* to biopsy (cohort A) or oligometastatic bone disease (≥1 to ≤ 4) at routine bone scan with at least one lesion amenable* to biopsy (cohort B)
*e.g. safely to biopsy and expectably providing sufficient tissue yield World Health Organisation (WHO) performance status 0 to 2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 months
- No prior local and/or systemic treatment for localised prostate cancer
- Willing to donate cancer tissue samples for research purposes (bone metastasis and primary tumour)
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to staff at the study site)
- Previous enrolment in the HYPROGEN study
- As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. uncompensated respiratory, cardiac, hepatic or renal disease)
- Evidence of any other significant clinical disorder or laboratory finding that made it undesirable for the patient to participate in the study
- Any investigational agents or study drugs from a previous clinical study within 30 days of the first tissue collection
- Prior treatment of localized prostate cancer including radiotherapy and/or androgen-deprivation therapy
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
- Contra-indications to MRI (incl. pacemakers etc.)
- Bone metastases in difficult to reach areas or areas which might be at risk for pathological fracture post biopsy as judged by biopsying radiologist / chief investigator
- Increased risk of bleeding as a result of biopsy
- History of bleeding disorders or thrombocytopenia (platelets <100/nL)
- Concomitant treatment with anticoagulant therapy, e.g. warfarin/low molecular weight heparin or Anti-Xa-inhibitors and other NOACs, if temporary cessation medically not justifiable
- Current urinary tract infection (UTI) or prostatitis
ARM 2
Inclusion Criteria:
- Male patients aged 18 years and older cT¬2-T3 / cN0-N1 / cM0 Any Group Grade (GG) 2-5: this includes Gleason scores 3+4, 4+3, 4+4, 4+5, 5+3, 5+4, 5+5. Any PSA
- Histologically proven adenocarcinoma of the prostate
- Undergoing radical prostatectomy as primary treatment for localised prostate cancer
- World Health Organisation (WHO) performance status 0 to 2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 months
- No prior local and/or systemic treatment for localised prostate cancer
- Willing to donate cancer tissue samples for research purposes (any metastasis and primary tumour)
Exclusion criteria:
- Involvement in the planning and/or conduct of the study (applies to staff at the study site)
- As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. uncompensated respiratory, cardiac, hepatic or renal disease)
- Any investigational agents or study drugs from a previous clinical study within 30 days of the first tissue collection
- Prior treatment of localized prostate cancer including radiotherapy and/or androgen-deprivation therapy
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
- Contra-indications to MRI (incl. pacemakers etc.)
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Arm 1
Arm 1 - De novo, treatment-naïve metastatic prostate cancer
|
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.
Other Names:
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.
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.
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.
Arm 1 -
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:
2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.
ARM 1 - 2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.
|
Arm 2
Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy
|
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.
Other Names:
Arm 1 -
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:
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.).
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary outcome measure
Time Frame: 24 months
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To document the differential genomic aberrations and gene expressional alterations in hormone-naïve primary prostate cancers and paired skeletal metastases with respect to the presence or abscence of tissue hypoxia in the tumour samples.
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24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary outcome measure
Time Frame: 24 months
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To determine extent of CTCs DNA in treatment naive metastatic prostate cancer in the presence or absence of hypoxia
|
24 months
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CFTSp155
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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