Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer

• Status: Not yet recruiting
• Trial end date: 2029-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

The study is an open label, multi-centre, randomized phase III study. The patients will be randomised in a 2:1 ratio to treatment consisting of

• Arm A: MD-SBRT in addition to standard treatment

• Arm B: Standard treatment

Study population: Patients with hormone sensitive prostate cancer (HSPC) with oligometastatic disease detected by PSMA-PET/DT. This includes patients with de novo oligometastatic HSPC and recurrent HSPC after primary RT or prostatectomy.

Primary endpoint: Failure free survival (time to castration resistant prostate cancer, CRPC)

Secondary endpoints:

• Predictive value of investigated biomarkers in blood and imaging

• Acute and late toxicity after MD-SBRT

• PROM at 3 months, 1, 3 and 5 years

• Overall survival

• Differences in outcome between patients by strata

Stratification: To avoid imbalance between treatment arms the minimisation method will be used to achieve balance between de novo oligo-metastatic and oligo-recurrent patients, as well as treatment site.

Safety evaluation: Adverse events and side effects graded according to CTCAE v5.0 will be collected every 6th month. Serious Adverse Events are to be reported within 24 hours throughout the study duration.

Statistical methods: Survival endpoints will be calculated using the Kaplan-Meier method with differences compared using the stratified log-rank test. Randomization time is set as baseline time. Pre-planned subgroup analysis will occur based on pre-specified stratification variables. A Cox multivariable regression model will be used to determine factors predictive of survival. Safety analysis will be performed with Mann-Whitney U-test or Fishers exact test.

Criteria for evaluation: Per protocol (patients that have started study treatment) and Intention to treat (all included patients).

Planned sample size: 114 patients

Analysis plan:

The primary end point will be analysed after pre-specified number of events have occurred or at 60 months of follow up. Safety analysis of acute toxicity will take place after median follow up of 6 months. Safety analysis of late toxicity will be analysed after study closure.

Duration of the study:

Three to five years inclusion. 60 months of follow-up after randomization of the last patient.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Umeå University
• Collaborators: Karolinska University Hospital; Region Jönköping County; Region Örebro County; Region Skane; Stockholm South General Hospital; University Hospital, Umeå; Vastra Gotaland Region
• Treatments: Androgens; Hormone Antagonists; Hormones

Criteria

Inclusion Criteria:

1. Histologically confirmed prostate cancer (ICD-O-3 C61)

2. WHO/ECOG performance status 0-1

3. 1-3 skeletal or extra pelvic lymph node metastases detected by PSMA-PET/CT in i. de novo prostate cancer or ii. PSA-relapse after definitive RT or prostatectomy

4. Willing and able to provide informed consent-

Exclusion Criteria:

1. Castration resistant prostate cancer (progression with castrate levels of testosterone <20ng/dL)

2. Any treatment known to affect PSA (including ADT) for prostate cancer within 6 months (exception: ADT started due to oligometastatic disease within 2 weeks of study entry)

3. Patient eligible for other treatment (e.g., early docetaxel) than standard treatment described in the protocol as judged by treating physician

4. Life expectancy <3 years by any reason, including concomitant or previous malignancies

5. Previous radiotherapy or surgery that may interfere with the planned treatment (including intra-prostatic recurrence if previous RT to the prostate)

6. > 3 PSMA-PET/CT positive target lesions (excluding the prostate in de novo patients or prostate bed post radical prostatectomy)

7. PSMA-PET verified metastases other than skeletal or lymph nodes

8. Metastases in base of scull and/or calotte

9. Any target lesions not treatable with image guided RT (IGRT) due to overlap with previous RT fields or exceeded dose constraint to OAR(s) as specified in study protocol