Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18+
SponsorKarin Soderkvist
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed prostate cancer (ICD-O-3 C61)
WHO/ECOG performance status 0-1
1-3 skeletal or extra pelvic lymph node metastases detected by PSMA-PET/CT in de novo prostate cancer or PSA-relapse after definitive RT or prostatectomy
Willing and able to provide informed consent-
Disqualifiers
Castration resistant prostate cancer (progression with castrate levels of testosterone)
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)
Patient eligible for other treatment (e.g., early docetaxel) than standard treatment described in the protocol as judged by treating physician
Life expectancy <3 years by any reason, including concomitant or previous malignancies
Trial design
Design model
Parallel
Treatments tested in this trial
stereotactic body radiotherapy
Radiation30 Gy in 3 fractions alternatively 40 Gy in 5 fractions delivered with stereotactic radiotherapy-principles
androgen deprivation therapy
Combination productMedical castration and next-generation Hormonal Agent along with radiotherapy to the prostate in de novo oligometastatic prostate cancer
Radiotherapy
RadiationRT to the prostate for de novo patients
Treatment groups
118 Participants
are divided into 2 treatment groupsGroup A: Standard of CareActive comparator 2 interventions
Group B: SBRT+Standard of CareExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Failure free survival
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.
Time frame
Throughout the study duration (72 months of follow up for last patient included.)Secondary outcomes
1
Number of participants with treatment-related adverse events as assessed by CTCAE v5.
Side effects according to Common Terminology Criteria for Adverse Events version 5, CTCAE v5 will be collected at baseline, 3 and 6 months after randomisation for all organs at risk within 3 cm from the SBRT-target in the electronic case report form. Adverse events are scored from 0 (none) to 5 (fatal) in the electronic case report form. We will report the number of patients with no reported side effects as well as the number of patients scoring 1, 2, 3, 4 and 5 assessed by CTCAE v5.
Time frame
Until 6 months after randomisation2
Number of participants with treatment-related serious adverse events as assessed by CTCAE v5.
Side effects grade 4 or higher according to Common Terminology Criteria for Adverse Events version 5, CTCAE v5 will be collected every 6th months after randomisation for all organs at risk within 3 cm from the SBRT-target. Adverse events are scored from 0 (none) to 5 (fatal) are collected in the electronic case report form. We will report the number of patients with no reported side effects as well as the number of patients scoring 1, 2, 3, 4 and 5 assessed by CTCAE v5.
Time frame
Throughout the study duration (72 months of follow up for last patient included.)3
Outcome prediction
Blood samples will be collected to enable evaluation of circulating biomarkers in relation to patient response to treatment at baseline, 1 and 3 months after randomisation, and at progression. Specifically, plasma will be sampled and circulating tumor cells and platelets will be further isolated. Imaging parameters from the baseline PSMA-PET/CT will also be evaluated in relation to outcome.
Time frame
Throughout the study duration (72 months of follow up for last patient included.)4
Patient reported quality of life assessed by EORTC-QLQ 30
Patients will fill out a cross validated self registration questionnaire; European Organistaion for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ 30, at baseline, 3 months, year 1, 3 and 5. The questionnaire consists of 28 statements that are to be graded from 1 (not at all) to 4 (very well) according to how well they correspond to the patients perception. EORTC QLQ30 also ask for the patient to score their overall sense of 1)health and 2)quality of life on a scale from 1 (very poor) to 7 (excellent).
Time frame
Throughout the study duration (72 months of follow up for last patient included.)Other outcomes
1
outcome according to strata
all outcomes 1-6 will be analysed by stata; primary or recurrent oligometastatic prostate cancer and study site (for inclusion)
Time frame
Throughout the study duration (72 months of follow up for last patient included.)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Karin Soderkvist
Lead sponsor
Umeå University
Sponsor institution
University Hospital, Umeå
Collaborator
Karolinska University Hospital
Collaborator
Stockholm South General Hospital
Collaborator
Region Skane
Collaborator
Ryhov County Hospital
Collaborator
Sahlgrenska University Hospital
Collaborator
Trondheim University Hospital
Collaborator
Capio Sankt Görans Hospital
Collaborator
Alesund Hospital
Collaborator
Region Örebro County
Collaborator
Source ClinicalTrials.gov