Clinical trial NCT05936736: 24 Gy in One Fraction Urethral-sparing "HDR Like" SBRT for Prostate Cancer
Official title: 24 Gy in One Fraction Urethral-sparing "High-Dose-Rate Like" Stereotactic Body RadioTherapy for Prostate Cancer: a Single-center Non-randomized Prospective Clinical Study (PRO-FAST)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Localized Prostate Carcinoma
Keywords: Prostate Cancer
Single fraction SBRT
Urethral sparing HDR like
PSMA PET/CT
Organ movement
Radiomics
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2023-07-10
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: According to the optimal design of Simon, 13 pts will be enrolled for the first phase of the study. Hypothesis: the proportion of pts free from acute cumulative G ≥3 toxicity (CTCAE v5.0 scale) 1 month after the end of treatment must be \< 85% to suspend treatment and \> 95% to consider the treatment as safe. The treatment will be interrupted if G3-G4 toxicities and/or biochemical recurrences are recorded within a month in 2 or more pts, otherwise the study will continue with the second phase enrolling another 52 pts for a total of 65 pts. A single fraction SBRT of 24 Gy with the "urethral sparing HDR like" technique will be delivered. Assuming a minimal drop-out, 5 more pts will be enrolled, thus reaching a total number of 70 pts (65 necessary + 5 for any drop-outs). In the absence of worse subsequent toxicity and with a biochemical control comparable to that in the literature as well as historical treatments of our department, the scheme will be considered as safe and effective.
Primary purpose: TREATMENT

Brief summary: Patients with prostate cancer who are candidates for stereotactic radiotherapy to the prostate and seminal vesicles will undergo staging exams, which will include prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT). If the PET scan is negative and the uroflowmetry is acceptable, the patients will perform the treatment, after fiducial implantation, simulation CT and magnetic resonance (MR), in a single fraction, delivered with a high-dose-rate (HDR)-like urethral sparing technique. In 70 patients, acute and late toxicity, biochemical control, overall survival, cancer specific-survival, and quality of life (through specific questionnaires) will be evaluated.

Detailed description: This is an interventional prospective non-randomised single-center trial that will enroll, 13 patients for the first phase of the study, according to the optimal design of Simon. The hypothesis is that the proportion of patients free from acute cumulative G3-G4 toxicity (Common Terminology Criteria for Adverse Events-CTCAE v5.0 scale) 1 month after the end of treatment must be \< 85% to suspend treatment and \> 95% to consider the treatment as safe.

The treatment will be interrupted if G3-G4 toxicities and/or biochemical recurrences are recorded within a month in 2 or more patients; otherwise the study will continue with the second phase. Another 52 patients will be added, for a total of 65 patients. The treatment consists in a single fraction of 24 Gy with the "urethral sparing HDR like" technique. Assuming a minimal drop-out, given that the primary endpoint is toxicity one month after treatment, we will enroll 5 more patients in total, thus reaching a total number of 70 patients (65 necessary + 5 for any drop-outs).

In the absence of worse subsequent toxicity, and with biochemical control comparable to that in the literature as well as historical treatments in our Radiation Oncology, the scheme will be considered safe, and the enrollment will continue open label.

Patients with negative lymph nodes and without distant metastases will be enrolled and treated on the prostate/prostate and tumor vesicles (depending on the stage) at a total dose of 24 Gy delivered in a single fraction, sparing the urethra and with a dose distribution similar to high dose rate brachytherapy. Androgen Deprivation Therapy (ADT) will be prescribed according to the guidelines for the stages of the disease.

Short-term cortisone and alpha lytics will be prescribed, for prophylactic purposes. Follow-up visits will be performed at 1, 3, 6,12,18, 24, 36, 48, 60 months with blood tests including prostate specific antigen (PSA) and testosterone (performed every 3 months in the first two years, every 6 months in the next 3 years), imaging, when needed, and quality of life questionnaires: European Organization for Research and Treatment of cancer (EORTC) quality of life questionnaire (QLQ) C30 and QLQ-PR25, International Prostate symptoms score (IPSS), International Index of Erectile Function (IIEF)-5, Expanded Prostate Cancer Index Composite (EPIC)- 26.

Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of prostate adenocarcinoma, International Society of Urological Pathology (ISUP) grade groups 1-5
* Patients over 18 years of age
* Signed informed consent
* Negative lymph nodes confirmed by imaging (PSMA PET/CT and/or pelvic MRI with and without contrast medium) where recommended by guidelines (intermediate and high risk patients, according to National Comprehensive Cancer Network (NCCN) guidelines) in the previous 3 months
* Clinical M0 (PSMA PET/CT and/or bone scan and/or pelvic MRI with and without contrast medium in suspected patients and unfavorable intermediate and high risk patients, according to NCCN guidelines), in the previous 3 months
* Acceptable uroflowmetry: peak urine flow index (peak flow preferably ≥ 15 ml/s), post voiding residue (PVR) ≤50 cc. If lower, acceptable if, by carrying out 3 months of neoadjuvant hormone therapy + alpha-lytic for the reduction of prostate volume, uroflowmetry is reset to at least ≥ 12 ml/s.
* PS (ECOG) ≤2
* No previous pelvic radiotherapy
* Other conditions necessary for the correct execution of the proposed treatment (ability to fill in the questionnaires for the evaluation of the Quality of Life EORTC QLQ-C30, EORTC QLQ-PR25, IPSS, IIEF-5, EPIC 26)

Exclusion Criteria:

* Serious systemic diseases
* Psychic or other disorders that may prevent the patient from signing the informed consent
* Previous invasive cancer, except skin cancer (excluding melanoma) unless patient free of disease for at least 3 years (e.g. carcinoma in situ of the oral cavity or bladder)
* Lymph node disease (N1)
* Evidence of distant metastases (M1)
* IPSS questionnaire data \> 20 points
* Uroflowmetry with maximum basal flow ≤ 11 ml/sec and/or PVR \>100 ml
* Concomitant urinary/gastrointestinal inflammatory diseases (e.g. ulcerative colitis, Crohn's disease)
* Overactive bladder
* Impossibility of implantation of fiducials
* Inability or refusal to place bladder catheter for simulation CT and MR
* Inability to perform simulation MRI
* Contraindication for hormonal treatment for patients with unfavorable intermediate, high or very high risk disease
* Non-compliance with dose limits established in the treatment plan

Primary outcomes:
measure: Acute toxicity
timeFrame: one month
Secondary outcomes:
measure: Biochemical control
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Biochemical relapse
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Local Control
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Distant Disease Control
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Survival
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Subacute Toxicity
timeFrame: 3 months
measure: Late Toxicity
timeFrame: 5 years (with interim analyzes at 1 and 3 years)
measure: Incidence of Treatment-Emergent Adverse Events as assessed with general quality of life questionnaires
timeFrame: 5 years
measure: Incidence of Treatment-Emergent Adverse Events as assessed with prostate specific quality of life questionnaires
timeFrame: 5 years
measure: Incidence of Treatment-Emergent Adverse Events as assessed with urinary quality of life questionnaires
timeFrame: 5 years
measure: Incidence of Treatment-Emergent Adverse Events as assessed with erectile quality of life questionnaires
timeFrame: 5 years
measure: Incidence of Treatment-Emergent Adverse Events as assessed with composite quality of life questionnaires
timeFrame: 5 years
Other outcomes:
measure: Organ movement
timeFrame: 3 years
measure: Radiomics
timeFrame: 5 years ( with interim analyzes at 3 years)
Locations:
city: Milan
country: Italy
facility: San Raffaele Scientific Institute
state: MI
Study officials:
affiliation: IRCCS San Raffaele Scientific Institute
name: Nadia Di Muzio, Prof
role: STUDY_DIRECTOR
affiliation: IRCCS San Raffaele Scientific institute
name: Andrei Fodor, MD
role: STUDY_CHAIR
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