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

Condition(s) studied

Investigational drug(s) / intervention(s)

stereotactic body radiotherapy: 30 Gy in 3 fractions alternatively 40 Gy in 5 fractions delivered with stereotactic radiotherapy-principles

androgen deprivation therapy: Medical castration and next-generation Hormonal Agent along with radiotherapy to the prostate in de novo oligometastatic prostate cancer

Radiotherapy: RT to the prostate for de novo patients

Study summary

The study is an open label, multi-centre, randomized phase III study. The patients will be randomised in a 1:1 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

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
* Castration resistant prostate cancer, CRPC
* 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: 118 patients

Analysis plan:

The primary end point will be analysed after pre-specified number of events have occurred. All patients randomised to SBRT will be followed minimum 60 months for toxicity. 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. 72 months of follow-up after randomization of the last patient.

Eligibility

Primary outcome measure(s)

• Failure free survival — Throughout the study duration (72 months of follow up for last patient included.)
  Time from randomisation to progressive disease. Progression is defined as 2 consecutive rises in blood PSA. PSA will be collected every third month and registered in the electronic case report form.

Trial sites (7)

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