Hypoxia-driven Prostate Cancer Genomics (HYPROGEN)

Recruiting

• Conditions: Prostate Cancer; Hypoxia
• Interventions: Drug: Optional non-IMP pimonidazole; Procedure: Radical Prostatectomy; Diagnostic Test: CT-guided Bone Biopsy; Diagnostic Test: TRUS-guided Targeted Transperineal Prostate Biopsy; Diagnostic Test: Prostate MRI scans; 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

• Registration Number: NCT05702619
• Lead Sponsor: The Christie NHS Foundation Trust

Brief 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.

Study Timeline

• Study Start: 2021-10-03
• Study First Submitted: 2022-11-03
• Status Verified: 2023-01
• Study First Submitted QC: 2023-01-26
• Last Update Submitted: 2023-01-26
• Study First Posted: 2023-01-27
• Last Update Posted: 2023-01-27
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 60

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm 1	Optional non-IMP pimonidazole	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 2	Optional non-IMP pimonidazole	Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy
Arm 2	Radical Prostatectomy	Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy
Arm 1	Whole-body MRI	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 1	TRUS-guided Targeted Transperineal Prostate Biopsy	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 1	Baseline bloods - for germline testing	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 1	Baseline bloods for CTCs and ct DNA taken at same time as baseline bloods in Arm 1	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 1	CT-guided Bone Biopsy	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 1	Post-pimonidazole bloods for CTCs and ctDNA	Arm 1 - De novo, treatment-naïve metastatic prostate cancer
Arm 2	Prostate MRI scans	Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy
Arm 2	Baseline bloods - for germline testing	Arm 2 - De novo, treatment- naïve localised prostate cancer planned for radical prostatectomy

Primary Outcome Measures

Name	Time	Method
Primary outcome measure	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 Measures

Name	Time	Method
Secondary outcome measure	24 months	To determine extent of CTCs DNA in treatment naive metastatic prostate cancer in the presence or absence of hypoxia

Trial Locations

Locations (1)

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom