Clinical trial NCT04983095: Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer
Official title: Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer Metastatic
Radiation Therapy
Positron-Emission Tomography
Keywords: Oligometastatic Prostate Cancer
Hormone Sensitive
Stereotactic Body Radiotherapy
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: University Hospital, Umeå
name: Karolinska University Hospital
name: Stockholm South General Hospital
name: Region Skane
name: Capio Sankt GÃ¶rans Hospital
name: Region Ã-rebro County
name: Ryhov County Hospital
name: Sahlgrenska University Hospital
First posted: 2021-07-30
Enrollment: 118
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomised to control (standard care)1:1 intervention (SBRT+standard care)
Primary purpose: TREATMENT

Brief 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.

Detailed description: Standard of Care (arm A and B): 3 years of ADT with the addition of abiraterone+prednisolone for two years. If the patient is de novo oligo-metastatic, RT to the prostate +/- pelvic fields is considered as standard treatment.

Study intervention (arm A): MD-SBRT to all PSMA-PET/CT positive metastatic target volume(s) with 30 Gy in 3 fractions or 40 Gy in 5 fractions in addition to SoC. For recurrent patients post prostatectomy with PSMA-PET-positive finding at prostate bed +/- regional lymph nodes (without prior local RT) salvage RT +/-pelvic fields with SIB to the PSMA+ GTV is to be delivered (sum of SBRT-targets maximum 3).

Screening procedure:Inclusion/exclusion criteria evaluation including evaluation of feasibility of SBRT to all positive lesions on PSMA-PET/CT performed within approx. 30 days of randomization.

Study specific procedure: Recording/collecting of baseline data including baseline PROM and pre-ADT testosterone and PSA. Standard treatment with ADT administered at randomization to all study patients. Abiraterone is initiated within 8 weeks of study entry. Start of MD-SBRT within approx. 28 days of randomization to patients in arm A. Additional RT as specified in study intervention started within 90 days. Follow up according to protocol, minimum 60 months.

Eligibility 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 de novo prostate cancer or 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)
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 and regional lymph node metastasis in de novo patients or prostate bed and or regional lymph node metastasis in recurrent patients)
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

Primary outcomes:
measure: Failure free survival
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.
timeFrame: Until 6 months after randomisation
measure: Number of participants with treatment-related serious adverse events as assessed by CTCAE v5.
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
measure: Outcome prediction
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
measure: Patient reported quality of life assessed by EORTC-QLQ 30
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
measure: Overall survival
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
measure: Castration resistent prostate cancer, CRPC
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
Other outcomes:
measure: outcome according to strata
timeFrame: Throughout the study duration (72 months of follow up for last patient included.)
Locations:
city: Stockholm
country: Sweden
facility: Capio St Göran Hospital
state: Region Stockholm
city: Stockholm
country: Sweden
facility: Södersjukhuset
state: Region Stockholm
city: Umeå
country: Sweden
facility: Umeå University hospital
state: Umea
city: Jönköping
country: Sweden
facility: Ryhovs county hospital
city: Lund
country: Sweden
facility: Region Skåne
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Örebro
country: Sweden
facility: Region Örebro Län
state: Örebro Län
Study officials:
affiliation: Region Västerbotten, Umeå University
name: Karin Söderkvist
role: PRINCIPAL_INVESTIGATOR
References: