Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Prostatic Neoplasms

Disease Attributes

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 30 Gy (5 sessions at a level of 6 Gy each- 1 session per day) 30 Gy is the first dose-level. During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 25 Gy (5 sessions at a level of 5 Gy each- 1 session per day) During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 36 Gy (6 sessions at a level of 6 Gy each- 1 session per day) During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

This radiotherapy may be administered with the CyberKnife® or a linear accelerator allowing stereotactic radiotherapy.

Stereotactic Body Radiotherapy

Soazig NENAN

Meryem BRIHOUM

Emmanuel MEYER

Geneviève LOOS

Magali QUIVRIN

David PASQUIER

Pascal POMMIER

Pascal Pommier

David AZRIA

Philippe MAINGON

Stéphane GUERIF

Renaud DE CREVOISIER

Stephane SUPIOT

Nicolas MAGNE

Guillaume JANORAY

Didier PEIFFERT

David Pasquier

Stereo-Re-Pro aims to provide further evidence of Stereotactic Body Radiotherapy (SBRT) as a supplementary non-invasive curative treatment for local recurrence following radiotherapy.

The objective of the first part of the trial (Phase I) is to select the recommended dose for salvage SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy) based on dose-limiting toxicity observed during the 18 weeks following the initiation of salvage-SBRT. Particular attention will be paid to the quality of life and tolerance of the treatment.

The objective of the second part of the trial (phase II) is to estimate the efficacy of the salvage-SBRT in terms of biochemical relapse-free survival rate.

To date, no standard local treatment exists for patients with an intraprostatic recurrence after radiotherapy. A number of treatments options exist including: radical prostatectomy, brachytherapy, High-intensity focused ultrasound (HIFU), cryotherapy, and stereotactic radiotherapy. These treatments are associated with a variety of genitourinary and gastrointestinal toxicities and complications. In recent years, stereotactic radiotherapy has been used to treat localized prostate cancer in the primary setting but also as a salvage treatment after failure of radiotherapy. The initial results of these studies are promising, with respect to survival and tolerance, but further studies are required to confirm these initial results.

The objective of STEREO-RE-PRO is to prospectively evaluate salvage SBRT for intraprostatic recurrent prostate cancer after primary external radiotherapy. This study will select patients for whom there is no standard local treatment.

After inclusion and non-inclusion criteria have been verified and the patient has consented, the site will register the screening and organize the baseline visit with the placement of fiducial markers within two months before the planned start of SBRT.

Once the fiducial placement has been performed and all eligibility criteria fully reviewed, the site will register the patient's participation so that the bio-statistician allocates the dose of SBRT. The dose will be allocated upon a model-based estimates provided by the statistical team and confirmed by the trial steering committee. Five or six fractions, at a level of 5 or 6 Gy per session (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), will be delivered over a maximum of 12 days to provide a total dose of 25 to 36 Gy. During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

A follow-up visit is planned at 6, 10, 18 weeks from the start of SBRT for safety evaluation. Subsequent follow-up visits are planned at 6, 9, 12, 18, 24, 30, and 36 months after the start of radiotherapy. Thereafter, yearly follow-up visits at 48, 60, and 72 months after starting SBRT will be planned after the initial 3-year follow-up period. M72 visit corresponds to the end of study visit.

Efficacy of Repeat Stereotactic Radiation in Patients With Intraprostatic Tumor Recurrence

Phase I/II Multi-center Study Evaluating the Efficacy of Repeat Stereotactic Radiation in Patients With Intraprostatic Tumor Recurrence After External Radiation Therapy

The dose-escalation part of the study will terminate once 10 patients have been treated and evaluated at a dose currently identified as the recommended dose.

Acute and late genitourinary toxicities over the first 3 years according to the NCI-CTCAE V4.03 classification (June 14th, 2010)

Clinical progression-free survival is defined as the time interval between the date of registration and the date of clinical progression (local progression assessed by the physical examination, or appearance of metastatic lesions) or death irrespective of the cause.

Quality of life will be evaluated based on the EORTC QLQ-C30. The Time Until Definitive Deterioration (TUDD) will be computed from registration until the first observation of a definitive deterioration of the quality of life, defined as a score decreased by 10 points (in the case of global health scale and functional scales) or increased by 10 points (in the case of symptom scales) compared to the score at baseline, without later improvement superior to 10 points compared to baseline score.

Quality of life will be evaluated based on the EORTC QLQ-PR25. The Time Until Definitive Deterioration (TUDD) will be computed from registration until the first observation of a definitive deterioration of the quality of life, defined as a score decreased by 10 points (in the case of global health scale and functional scales) or increased by 10 points (in the case of symptom scales) compared to the score at baseline, without later improvement superior to 10 points compared to baseline score.

UNICANCER

SBRT: 5 x 6.75 Gy (every other day) to the total dose of 33.75 Gy

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

Wojciech Majewski, MD, PhD

Aleksandra Napieralska, MD, PhD

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.

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

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

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

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

Biochemical Control will be defined as observations without biochemical recurrence defined as PSA concentration:

1. \>2 ng/mL above the nadir (according to Phoenix) for groups A and C
2. \>0.2 ng/ml (according to AUA) for group B

Decrease in PSA level below baseline (pre-SBRT)

Metastases-Free Survival is the time interval between SBRT and ocurrence of distant metastases or death irrespective of the cause

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

Overall Survival is the time interval between SBRT and patient death irrespective of the cause

Evaluation of EORTC QLQ-C30 and PR-25 questionnaires

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy of Repeat Stereotactic Radiation in Patients With Intraprostatic Tumor Recurrence	NCT03438552	Local Recurrenc...	Stereotactic Bo...	18 Years -	UNICANCER
Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy	NCT06201078	Local Recurrenc... Radiotherapy	Stereotactic Bo...	18 Years - 80 Years	Maria Sklodowska-Curie National Research Institute of Oncology

Spots Global Cancer Trial Database for local recurrence of malignant tumor of prostate