Towards Optimal Treatment for High Risk Prostate Cancer (HYPOPRIME)

Towards Optimal Treatment for High Risk Prostate Cancer; Stereotactic Pelvic Radiotherapy With Focal Boost to the Primary Tumour

The goal of this clinical trial is to combine several optimized treatments of high risk prostate cancer. The main question to answer is: is it safe to combine these optimized treatments.

• patients will be irradiated on the prostate and (elective) lymph nodes more concentrated but with fewer hospital visits (hypofractionation)
• the tumor will get a higher dose
• androgen deprivation therapy will be reduced as much al possible preventing side effects

Researchers will compare oncological outcome and toxicity.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Prostate Carcinoma
• Intervention / Treatment: Radiation: HYPOPRIME treatment

Detailed Description

Rationale: Recently several randomized trial have shown benefits of changes made to radiotherapy of (high risk) localized prostate cancer patients: A focal boost was shown to improve outcome in men with intermediate/high risk prostate cancer (FLAME trial). Elective lymph node irradiation was shown to improve outcome in high risk prostate cancer patients (POP-RT). (Extreme) hypo fractionation was shown to be safe for low/intermediate risk prostate cancer patients. In addition: the added benefit of ADT (with substantial toxicity) seems reduced with improvements made to treatment and diagnosis in recent years (DART 01/05); own recent work on this topic; to be published)). None off the above were combined into one ideal treatment for high risk prostate cancer.

Objective: Determine the safety (oncological outcome and toxicity) of an comprehensive treatment combining recent advances in the treatment of high risk prostate cancer.

Study design: prospective cohort study with matched contemporary control group Study population: Men with high risk prostate cancer with an indication for elective lymph node irradiation Intervention: hypo fractionated pelvic radiotherapy with boost to primary tumour in the prostate Main study parameters/endpoints: biochemical recurrence free survival and late toxicity Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The additional burden of the study is considered to be low, as additional tests or site visits in comparison to current clinical follow up are not planned. Regarding safety, different parts of the investigational treatment were already shown to be safe in previous studies. The current study aims to combine these different parts into one treatment. We estimate that the risks associated with combining these treatments are very limited.

• Study Type: Interventional
• Enrollment (Estimated): 207
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ursula J Fisscher, PhD; Phone Number: +31 88 9792357; Email: u.fisscher@haaglandenmc.nl
• Study Contact Backup: Name: Mirjam E Mast, PhD; Phone Number: +31 88 9792357; Email: m.mast@haaglandenmc.nl

Study Locations

• Netherlands
  • Zuid Holland
    • Leidschendam, Zuid Holland, Netherlands, 2262 BA
      • Haaglanden Medical Centre
      • Contact: Mirjam E Mast, PhD; Phone Number: +31 88 9792357; Email: m.mast@haaglandenmc.nl
      • Contact: Carmen P Liskamp, MD; Phone Number: +31 88 9792357; Email: c.liskamp@haaglandenmc.nl
      • Principal Investigator: Leonard P Bokhorst, MD, PhD
      • Sub-Investigator: Carmen P Liskamp, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men (aged ≥18 years of age) diagnosed within 6 months before inclusion with high risk prostate cancer:

  • T3 based on digital rectal examination AND/OR
  • Grade >= 4 AND/OR
  • PSA >=20 ug/L
• Indication for elective lymph node irradiation (based on current clinical guidelines) OR N1 on imaging (with a maximum of 4 suspect lymph nodes)

Exclusion Criteria:

• Prior pelvic radiotherapy
• TransUrethral Resection of the Prostate (TURP) < 3 months ago
• Prostatectomy or other primary treatment for prostate cancer (e.g. HIFU, cryotherapy, etc)
• contraindications to MRI
• no visible lesion on MRI in prostate for boost
• no PSMA-PET scan
• inflammatory bowel disease
• metastatic disease (M1)
• PSA >50
• unsuitable for SBRT or WPRT
• medical history of cancer other than basal cell carcinoma of the skin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HYPOPRIME treatment; Hypo fractionated pelvic radiotherapy with boost to primary tumour in the prostate with elective lymph node irradiation and minimized androgen deprivation therapy	Radiation: HYPOPRIME treatment; Hypo fractionated pelvic radiotherapy with boost to primary tumour in the prostate with elective lymph node irradiation and minimized androgen deprivation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical recurrence free survival	rise of PSA 2 ng/ml above nadir	5 years
Late gastrointestinal and genito-urinary toxicity, and erectile dysfunction	according to CTC-AE v5	at 6 months and 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	5 years
Metastasis free survival	Metastasis free survival	5 years
Pattern of failure	based on PSMA in case of biochemical recurrence	5 years

Collaborators and Investigators

• Sponsor: Haaglanden Medical Centre
• Collaborators: Tata Memorial Centre
• Investigators: Principal Investigator: Leonard P Bokhorst, MD, PhD, Haaglanden Medical Centre

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): December 18, 2032
• Study Completion (Estimated): December 18, 2032

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: hypo fractionation; elective lymph node irradiation; focal boost; androgen deprivation therapy reduction
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: P23.081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No