Clinical trial NCT06201078: Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy
Official title: Phase II Study - Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy - PROSTARE (PROstate Cancer STereotActic REirradiation) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Local Recurrence of Malignant Tumor of Prostate
Radiotherapy
Keywords: local recurrence
prostate
radiotherapy
salvage
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2024-01-11
Enrollment: 55
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to evaluate the toxicity and efficacy of re-irradiation using focal stereotactic body radiotherapy (SBRT) in patients with local recurrence of prostate cancer after definitive or post-operative radiotherapy.

The main question is the tolerance of such treatment, concerning the incidence of Grade ≥ 2 and Grade ≥ 3 GU and GI toxicity. Also the efficacy of SBRT will be measured in terms of Biochemical Control with other secondary endpoints which include: Biochemical Response, Biochemical Failure-Free Survival, Metastases-Free Survival, Relapse-Free Survial, Local Control, Overall Survival and patients' reported tolerance measured with Quality of Life questionnaires (QoL C-30 and PR-25).

The evaluation of the tolerance and effectiveness of stereotactic radiotherapy (SBRT) will be performed in 3 subgroups: in patients with local recurrence after conventionally fractionated/moderately hypofractionated definitive radiotherapy (Group A) or ultrahypofractionated definitive SBRT (Group C) or after prostatectomy and post-operative radiotherapy (Group B).

The study group is planned to include 55 patients.

Detailed description: The diagnosis of local recurrence after radiotherapy in patients with prostate cancer is a serious clinical problem. Interventional salvage treatment in the previously irradiated area is difficult with safety issues of special concern. According to the MASTER meta-analysis the effectiveness of various local salvage methods turned out to be comparable in patients with local recurrence after definitive radiotherapy. Stereotactic radiotherapy (SBRT) had the best toxicity profile, so this non-invasive treatment may be a suitable alternative to other methods. A particular problem is local recurrences after post-prostatectomy radiotherapy. The data on SBRT in such setting are even more scarce than in the case of relapses after definitive radiotherapy. Still, they show a low percentage of serious adverse events of grade ≥3 and good treatment tolerance.

Considering the own experience with re-irradiation of patients with prostate cancer, it was decided that re-irradiation should be carried out in the form of focal SBRT. With the objective of enhancing the safety and quality of salvage re-irradiation, and a comprehensive evaluation of the efficacy of this treatment it was determined that it should be implemented as a prospective phase II study- PROSTARE (PROstate cancer STereotActic Reirradiation).

The evaluation of the tolerance and effectiveness of stereotactic radiotherapy (SBRT) will be performed in patients with local recurrence after conventionally fractionated/moderately hypofractionated definitive radiotherapy (Group A), ultrahypofractionated definitive SBRT (Group C), or after prostatectomy and postoperative radiotherapy (Group B).

The study will be conducted as a single-centre study. The evaluation of the safety and effectiveness of such treatment could help develop qualification criteria for repeated irradiation. As a consequence, this should allow for the implementation of this form of treatment into radiotherapy protocols and then, in a controlled and safe way, into clinical practice.

The total sample size will comprise 55 patients. The expected recruitment period is 6 years (10 patients per year).

Requirements for reirradiation with SBRT:

1. Both PET-PSMA and MR of the prostate or prostate bed are required in patients with recurrence after definitive radiotherapy or surgery followed by radiotherapy
2. Fiducial implantation is not routinely required
3. Empty rectum and partially empty/partially filled bladder (improved reproducibility)\* during treatment planning and during each fraction of stereotactic radiotherapy
4. Treatment with a linear accelerator is preferred
5. CBCT must be performed before each fraction of SBRT with verification for tumour location (GTV)\*\*
6. Focal radiotherapy, i.e., irradiation of only the visible tumour with an appropriate margin
7. Hormonal treatment is not routinely recommended (according to the ESTRO ACROP consensus) - up to the decision of the attending physician

   * Principles of preparation with laxatives - Bisacodyl is advocated 4-5 hours before SBRT. If the diameter of the rectum on the CT for treatment planning exceeds 4 cm in diameter, the procedure should be repeated after appropriate preparation of the patient.

     * If stereotactic radiotherapy is conducted on the CyberKnife - KV imaging and Tracking verification are required; additionally an assessment of bladder filling in ultrasonography should be performed

Eligibility criteria: Inclusion Criteria:

1. Local recurrence of prostate cancer after definitive radiotherapy

   1. biopsy proven or/and
   2. Consistent MRI and PET-PSMA results and PSA growth dynamics
2. Time since primary radiotherapy - at least 2 years
3. Good performance status (ZUBROD 0-1)

   * If the results of the MRI and PET PSMA are inconsistent, and if there is no technical possibility of performing an MRI biopsy, the treatment is acceptable, but repeated imaging (PET or MRI) should be performed to assess the dynamics of the recurrence.

Exclusion Criteria:

1. Polymetastatic dissemination in distant or regional lymph nodes (N1, M1) or oligometastatic dissemination, but not eligible for local forms of metastasis directed therapy (MDT)
2. Tumour volume (GTV) \> 14 cc
3. Poor tolerability of primary radiotherapy (≥G3 toxicity) or persistent late toxicity ≥G2 interfering with re-irradiation
4. Severe dysuria before repeated SBRT (e.g., IPSS ≥19)
5. Diseases of the distal part of the rectum or anal canal that may affect SBRT tolerance (e.g., anal fissure)
6. Previous prostate brachytherapy
7. Substantial risk for further urologic interventions (e.g., TURB/TURP)

Primary outcomes:
measure: Tolerance of salvage SBRT
timeFrame: 3 months post-SBRT, 2-years post-SBRT
Secondary outcomes:
measure: Tolerance of salvage SBRT
timeFrame: 3 months post-SBRT, every 6 months post SBRT up to 3-years post-SBRT
measure: Biochemical Control
timeFrame: 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT
measure: Biochemical Response
timeFrame: 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
measure: Biochemical Failure-Free Survival (BFS)
timeFrame: 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT
measure: Metastases-Free Survival
timeFrame: 1-year post SBRT, then annually up to 5-years post-SBRT
measure: Relapse-Free Survival
timeFrame: 1-year post SBRT, then annually up to 5-years post-SBRT
measure: Local Control
timeFrame: 1-year post SBRT, then annually up to 5-years post-SBRT
measure: Overall Surival
timeFrame: 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
measure: Patients' reported Quality of Life
timeFrame: 2-years post SBRT, 3-years post SBRT
Other outcomes:
Locations:
city: Gliwice
country: Poland
facility: Maria Sklodowska Memorial Research Institute of Oncology
Study officials:
affiliation: Maria Sklodowska Curie Memorial Research Institute of Oncology
name: Wojciech Majewski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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