Hypoxia-driven Prostate Cancer Genomics (HYPROGEN) (HYPROGEN)
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ClinicalTrials.gov Identifier: NCT05702619 |
Recruitment Status :
Recruiting
First Posted : January 27, 2023
Last Update Posted : January 27, 2023
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Condition or disease | Intervention/treatment |
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Prostate Cancer Hypoxia | Drug: Optional non-IMP pimonidazole Diagnostic Test: CT-guided Bone Biopsy Diagnostic Test: TRUS-guided Targeted Transperineal Prostate Biopsy Procedure: Radical Prostatectomy Diagnostic Test: Whole-body MRI Diagnostic Test: Prostate MRI scans 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 |
Study Type : | Observational |
Estimated Enrollment : | 60 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Hypoxia-driven Prostate Cancer Genomics (HYPROGEN) - Illuminating the Genomic Landscape of Hypoxia-driven Early Metastatic Prostate Cancer |
Actual Study Start Date : | October 3, 2021 |
Estimated Primary Completion Date : | June 30, 2023 |
Estimated Study Completion Date : | June 30, 2023 |
Group/Cohort | Intervention/treatment |
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Arm 1
Arm 1 - De novo, treatment-naïve metastatic prostate cancer
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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.
Other Name: Pimonidazole Hydrochloride 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. 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. Other: Baseline bloods - for germline testing 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:
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. |
Arm 2
Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy
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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.
Other Name: Pimonidazole Hydrochloride 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: 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 -
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:
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- Primary outcome measure [ Time Frame: 24 months ]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.
- Secondary outcome measure [ Time Frame: 24 months ]To determine extent of CTCs DNA in treatment naive metastatic prostate cancer in the presence or absence of hypoxia
Biospecimen Retention: Samples With DNA
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
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
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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.)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05702619
Contact: Martin Swinton | 07896026629 | m.swinton@nhs.net | |
Contact: Fizzah M Ali | fizzah.ali@manchester.ac.uk |
United Kingdom | |
The Christie NHS Foundation Trust | Recruiting |
Manchester, United Kingdom | |
Contact: Martin Swinton m.swinton@nhs.net | |
Contact: Fizzah M Ali fizzah.ali@manchester.ac.uk |
Responsible Party: | The Christie NHS Foundation Trust |
ClinicalTrials.gov Identifier: | NCT05702619 |
Other Study ID Numbers: |
CFTSp155 |
First Posted: | January 27, 2023 Key Record Dates |
Last Update Posted: | January 27, 2023 |
Last Verified: | January 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
genomic multi-omic |
Prostatic Neoplasms Hypoxia Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms |
Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Signs and Symptoms, Respiratory |