Trial Title:
Hypoxia-driven Prostate Cancer Genomics (HYPROGEN)
NCT ID:
NCT05702619
Condition:
Prostate Cancer
Hypoxia
Conditions: Official terms:
Prostatic Neoplasms
Hypoxia
Conditions: Keywords:
genomic
multi-omic
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
Optional non-IMP pimonidazole
Description:
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.
Arm group label:
Arm 1
Arm group label:
Arm 2
Other name:
Pimonidazole Hydrochloride
Intervention type:
Diagnostic Test
Intervention name:
CT-guided Bone Biopsy
Description:
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.
Arm group label:
Arm 1
Intervention type:
Diagnostic Test
Intervention name:
TRUS-guided Targeted Transperineal Prostate Biopsy
Description:
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.
Arm group label:
Arm 1
Intervention type:
Procedure
Intervention name:
Radical Prostatectomy
Description:
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.).
Arm group label:
Arm 2
Intervention type:
Diagnostic Test
Intervention name:
Whole-body MRI
Description:
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 group label:
Arm 1
Intervention type:
Diagnostic Test
Intervention name:
Prostate MRI scans
Description:
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.
Arm group label:
Arm 2
Intervention type:
Other
Intervention name:
Baseline bloods - for germline testing
Description:
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
Arm group label:
Arm 1
Arm group label:
Arm 2
Intervention type:
Other
Intervention name:
Baseline bloods for CTCs and ct DNA taken at same time as baseline bloods in Arm 1
Description:
2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC)
collection and circulating tumour DNA (ctDNA) extraction.
Arm group label:
Arm 1
Intervention type:
Other
Intervention name:
Post-pimonidazole bloods for CTCs and ctDNA
Description:
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 group label:
Arm 1
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.
Criteria for eligibility:
Study pop:
Arm 1 - De novo, treatment-naïve metastatic prostate cancer Arm 2 - De novo, treatment-
naïve localised prostate cancer planned for radical prostatectomy
Sampling method:
Non-Probability Sample
Criteria:
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.)
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Martin Swinton
Email:
m.swinton@nhs.net
Contact backup:
Last name:
Fizzah M Ali
Email:
fizzah.ali@manchester.ac.uk
Start date:
October 3, 2021
Completion date:
June 30, 2023
Lead sponsor:
Agency:
The Christie NHS Foundation Trust
Agency class:
Other
Collaborator:
Agency:
Prostate Cancer UK
Agency class:
Other
Source:
The Christie NHS Foundation Trust
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05702619
