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

NCT ID: NCT04983095

Last Updated: 2024-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-27

Study Completion Date

2033-12-31

Brief Summary

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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

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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.

Conditions

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Prostate Cancer Metastatic Radiation Therapy Positron-Emission Tomography

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients are randomised to control (standard care)1:1 intervention (SBRT+standard care)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care

ADT+ARPI to all patients and local RT +/- pelvic fields to de novo patients

Group Type ACTIVE_COMPARATOR

androgen deprivation therapy

Intervention Type COMBINATION_PRODUCT

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

Radiotherapy

Intervention Type RADIATION

RT to the prostate for de novo patients

SBRT+Standard of Care

SBRT to all PSMA+ lesions in addition to SoC and salvage RT to the prostate bed +/- pelvic fields if recurrent post prostatectomy and PSMA-PET+ in the pelvis

Group Type EXPERIMENTAL

stereotactic body radiotherapy

Intervention Type RADIATION

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

androgen deprivation therapy

Intervention Type COMBINATION_PRODUCT

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

Radiotherapy

Intervention Type RADIATION

RT to the prostate for de novo patients

Interventions

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stereotactic body radiotherapy

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

Intervention Type RADIATION

androgen deprivation therapy

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

Intervention Type COMBINATION_PRODUCT

Radiotherapy

RT to the prostate for de novo patients

Intervention Type RADIATION

Other Intervention Names

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stereotactic ablative radiotherapy image guided radiotherapy gonadotropin releasing hormone-agonist gonadotropin releasing hormone-antagonist androgen-receptor pathway inhibitor (ARPI) external radiotherapy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Umeå

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role collaborator

Stockholm South General Hospital

OTHER

Sponsor Role collaborator

Region Skane

OTHER

Sponsor Role collaborator

Capio Sankt Görans Hospital

UNKNOWN

Sponsor Role collaborator

Region Ã-rebro County

UNKNOWN

Sponsor Role collaborator

Ryhov County Hospital

OTHER

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

Karin Soderkvist

OTHER

Sponsor Role lead

Responsible Party

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Karin Soderkvist

Senior Consultant, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Karin Söderkvist

Role: PRINCIPAL_INVESTIGATOR

Region Västerbotten, Umeå University

Locations

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Region Skåne

Lund, Lund, Sweden

Site Status RECRUITING

Capio St Göran Hospital

Stockholm, Region Stockholm, Sweden

Site Status RECRUITING

Södersjukhuset

Stockholm, Region Stockholm, Sweden

Site Status RECRUITING

Karolinska University Hospital

Stockholm, Stockholm County, Sweden

Site Status RECRUITING

Umeå University hospital

Umeå, Umea, Sweden

Site Status RECRUITING

Ryhovs county hospital

Jönköping, , Sweden

Site Status RECRUITING

Region Örebro Län

Örebro, Örebro County, Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Karin Söderkvist, MD,PhD

Role: CONTACT

+46 90 7853222

Facility Contacts

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Adalsteinn Gunnlaugsson, Senior Consultant

Role: primary

Martina Westin, Senior Consultant

Role: primary

Chunde Li, Senior Consultant

Role: primary

Mattias Hedman, MD

Role: primary

Karin Söderkvist

Role: primary

0705282558

Kirsten Bjornlinger, M.D

Role: primary

Jenny Kahlmeter-Brandell, Senior Consultant

Role: primary

Related Links

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https://cancercentrum.se/samverkan/vara-uppdrag/forskning/cancerstudier-i-sverige/

Official site for clinical trials by Swedish Regional Cancer Centres in Collaboration

Other Identifiers

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METRO_vers1

Identifier Type: -

Identifier Source: org_study_id

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