Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy

Radiotherapy Clinical Trial

— PROSTARE  

Official title:

Phase II Study - Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy - PROSTARE (PROstate Cancer STereotActic REirradiation) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06201078
• Other study ID #: nio-kb/430-72/23
• Status: Recruiting
• Phase: Phase 2
• Start date: July 31, 2023
• Est. completion date: December 31, 2029

Study information

• Verified date: November 2023
• Source: Maria Sklodowska-Curie National Research Institute of Oncology
• Contact: Wojciech Majewski, MD, PhD
• Phone: +48322788001
• Email: wojciech.majewski[@]gliwice.nio.gov.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Secondary endpoints include: Biochemical Response, Metastases-Free Survival, Relapse-Free Survial, 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 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 60 patients.

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 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 60 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 empty/partially empty 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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 =15)

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)

Related Conditions & MeSH terms

• Local Recurrence of Malignant Tumor of Prostate
• Prostatic Neoplasms
• Radiotherapy
• Recurrence

Intervention

Radiation:
• Stereotactic Body Radiotherapy
Salvage SBRT will be performed in three subgroups of patients with local recurrence: Group A - after conventionally fractionated definitive radiotherapy; Group B - after prostatectomy and postoperative radiotherapy; Group C - after ultrahypofractionated definitive SBRT Target volumes: GTV- tumour visible on MRI and PET-CT; CTV- 1-3 mm margin around GTV PTV- 3 mm around CTV* *- in cases in which very high accuracy and reproducibility of SBRT are ensured, and the margin overlaps the rectum and/or bladder, it is possible to reduce the margin from these organs to 1 mm. Dose constrains: The criteria for limiting the dose in nearby organs are not well-defined for repeated irradiation - the following doses should be aimed: Maximum rectal dose =103% of the prescribed dose (optimal =100%) Maximum bladder dose =105% of the prescribed dose (optimal =103%) Dose-volume constrains: Rectum: • D30% <15Gy Bladder: • D30% < 15 Gy

Locations

Country	Name	City	State
Poland	Maria Sklodowska Memorial Research Institute of Oncology	Gliwice

Sponsors (1)

Lead Sponsor	Collaborator
Maria Sklodowska-Curie National Research Institute of Oncology

Country where clinical trial is conducted

Poland, 

References & Publications (5)

Archer P, Marvaso G, Detti B, Colombo F, Francolini G, Vandendorpe B, Thananayagam MA, Baty M, De Crevoisier R, Alongi F, Nicosia L, Scher N, Toledano A, Di Muzio N, Fodor A, Zilli T, Franzese C, Scorsetti M, Shelan M, Triggiani L, Aymes E, Le Deley MC, Jereczek-Fossa BA, Pasquier D. Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study. Eur Urol Oncol. 2023 Jun;6(3):303-310. doi: 10.1016/j.euo.2023.03.005. Epub 2023 Apr 1. — View Citation

Jereczek-Fossa BA, Marvaso G, Zaffaroni M, Gugliandolo SG, Zerini D, Corso F, Gandini S, Alongi F, Bossi A, Cornford P, De Bari B, Fonteyne V, Hoskin P, Pieters BR, Tree AC, Arcangeli S, Fuller DB, Franzese C, Hannoun-Levi JM, Janoray G, Kerkmeijer L, Kwok Y, Livi L, Loi M, Miralbell R, Pasquier D, Pinkawa M, Scher N, Scorsetti M, Shelan M, Toledano A, van As N, Vavassori A, Zilli T, Pepa M, Ost P; on the behalf of the European Society for Radiotherapy, Oncology Advisory Committee on Radiation Oncology Practice (ESTRO ACROP). Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus. Cancer Treat Rev. 2021 Jul;98:102206. doi: 10.1016/j.ctrv.2021.102206. Epub 2021 Apr 20. — View Citation

Miszczyk M, Kraszkiewicz M, Moll M, Kaminiow K, Sobel S, Dolla L, Wojcieszek P, Rajwa P, Yanagisawa T, Nowicka Z, Shariat SF, Goldner G, Miszczyk L, Majewski W. Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity. Cancers (Basel). 2023 Feb 13;15(4):1180. doi: 10.3390/cancers15041180. — View Citation

Schroder C, Tang H, Windisch P, Zwahlen DR, Buchali A, Vu E, Bostel T, Sprave T, Zilli T, Murthy V, Forster R. Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review. Cancers (Basel). 2022 Jan 29;14(3):696. doi: 10.3390/cancers14030696. — View Citation

Valle LF, Lehrer EJ, Markovic D, Elashoff D, Levin-Epstein R, Karnes RJ, Reiter RE, Rettig M, Calais J, Nickols NG, Dess RT, Spratt DE, Steinberg ML, Nguyen PL, Davis BJ, Zaorsky NG, Kishan AU. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. 2021 Sep;80(3):280-292. doi: 10.1016/j.eururo.2020.11.010. Epub 2020 Dec 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerance of salvage SBRT	Assessment of early and late radiation toxicity: Grade = 2 and = 3 radiation-induced bladder/urethral (GU) and bowel/rectal (GI) adverse events toxicity or other, according to CTCAE criteria	3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
Primary	Biochemical Control after salvage SBRT	Biochemical Control will be defined as observations without biochemical recurrence defined as PSA concentration: >2 ng/mL above the nadir (according to Phoenix) for groups A and C; >0.2 ng/ml (according to AUA) for group B	3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
Secondary	Biochemical Response	Decrease in PSA level below baseline (pre-SBRT)	3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
Secondary	Metastases-Free Survival	Metastases-Free Survival is the time interval between SBRT and ocurrence of distant metastases or death irrespective of the cause	1-year post SBRT, then annually up to 5-years post-SBRT
Secondary	Relapse-Free Survival	Relapse-Free Survival is the time interval between SBRT and ocurrence of clinical relapse: local recurrence, regional or distant metastases, start of hormonal therapy, or death irrespective of the cause	1-year post SBRT, then annually up to 5-years post-SBRT
Secondary	Overall Surival	Overall Survival is the time interval between SBRT and patient death irrespective of the cause	3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT
Secondary	Patients' reported Quality of Life	Evaluation of EORTC QLQ-C30 and PR-25 questionnaires	2-years post SBRT, 3-years post SBRT