Twice High Dose External Beam Radiotherapy by Image-guided Tomotherapy for Organ-confined Prostate Cancer Treatment Emulating High Dose Radiation (HDR) Brachytherapy

Study Overview
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Brief Summary
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Feasibility trial of twice high dose radiotherapy using Tomotherapy in patients with organ confined Prostate Cancer histologically proven. The study involves 2 steps: A) Assessment of safety as proportion of patients with acute ≥G3 Genito-urinary (GU) and Gastro-intestinal (GI) side effects on the first 16 enrolled patients; B) evaluation of primary and secondary objectives on overall patients.

Detailed Description
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Twice High dose external beam Radiotherapy by Image-guided tomotherapy for organ-confined Prostate cancer treatment emulating HDR brachytherapy: Feasibility trial of twice high dose radiotherapy using Tomotherapy in patients with organ confined Prostate Cancer histologically proven. The study involves 2 steps: A) Assessment of safety as proportion of patients with acute ≥G3 Genito-urinary (GU) and Gastro-intestinal (GI) side effects on the first 16 enrolled patients; B) evaluation of primary and secondary objectives on overall patients. Thirty-one patients will be enrolled, with histologically confirmed very low , low and intermediate risk prostate cancer following the National Comprehensive Cancer Network (NCCN) risk categories guidelines. Patient should not be eligible to prostatectomy or patient's should refuse to undergo surgery. Prescription dose to the target: 20-23 Gy in 2 fractions on the whole prostate gland +/- seminal vesicles and 24-27 Gy in 2 fractions as simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL) 2 weeks in all.

Official Title
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Twice High Dose External Beam Radiotherapy by Image-guided Tomotherapy for Organ-confined Prostate Cancer Treatment Emulating HDR Brachytherapy: Single Institution Feasibility Study

Conditions
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Prostate Adenocarcinoma, Radiotherapy; Complications, Tomotherapy

Intervention / Treatment
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* Radiation: tomotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate adenocarcinoma (a diagnostic biopsy with at least 10 cores is needed) Low and intermediate-risk NCCN risk categories: low-risk ( cT1-2a, Gleason Score ≤ 6 PSA <10 ng/ml) and among those with intermediate-risk features (clinical stage T2b-c or GS 7 or PSA 10-20 ng/ml) those patients with favorable ones (a single factor for intermediate risk and GLS 3 + 4 and <50% of biopsy cores containing cancer) will be selected. (30). Age ≥18 years Good performance status , Eastern Cooperative Oncology Group (ECOG) < 2) or Karnofsky performance status (KPS) > 70 No previous pelvic RT Patient not eligible to prostatectomy or patient's refusal to undergo surgery. NO previous prostatectomy or TURP Good urinary flow (peak flow ≥ 10 ml/s) Previous ADT is permitted Prostate size ≤ 60 cc International Prostate Symptom Score ≤ 15 Male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Nodal involvement or distant metastases (cN1 or cM1) Extracapsular tumor or locally advanced disease (cT3-cT4) IPSS questionnaire > 20 Concomitant inflammatory bowel Prior history of chronic prostatitis Prior history of urethral stricture Important systemic diseases or oral anticoagulant therapy ongoing Non-conformity to dose constraints at the treatment planning Other invasive cancer (apart from non-melanoma skin), unless the patient has been free from disease for at least 3 years; Abnormal complete blood count. Any of the following: platelet count less than 75,000/ml, Hb level less than 10 gm/dl, WBC less than 3.5/ml, abnormal renal function tests (creatinine > 1.5), severe renal impairment (GFR less than 30) Placement of pacemakers and metallic vascular clips (all contraindication to performing prostate mpMRI).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Feasibility trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose external beam Radiotherapy<br>Image-guided tomotherapy | Radiation: tomotherapy<br>* 20-23 Gy in 2 fractions on the whole prostate gland +/- seminal vesicles and 24-27 Gy in 2 fractions as simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL) 2 weeks in all.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of Grade ≥3 early GU toxicity | Early Grade ≥3 GU toxicity measured by Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer (RTOG/EORTC) toxicity scale, using a scoring range from 0 to 5 for, where 0 means an absence of radiation effects and 5 means the effects led to death | within 3 months after end of Radiotherapy | 
| occurrence of Grade ≥3 early GI toxicity | Early Grade ≥3 GI toxicity measured by Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer (RTOG/EORTC) toxicity scale, using a scoring range from 0 to 5 for, where 0 means an absence of radiation effects and 5 means the effects led to death | within 3 months after end of Radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Grade ≥3 Late GU toxicity | Late Grade ≥3 GU toxicity measured by Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer (RTOG/EORTC) toxicity scale, using a scoring range from 0 to 5 for, where 0 means an absence of radiation effects and 5 means the effects led to death | more than 6 months after end of Radiotherapy | 
| Evaluation of Prostate Antigen Serum (PSA) failure | Evaluation of PSA failure is defined according to the Consensus Statement of the American Society of Radiation Oncology (ASTRO) as elevation of PSA levels nadir +2 ng/ml and confirmed by one measurement (Phoenix criterion) or biochemical response through trimestral PSA level evaluation. | up to 8 years | 
| Time to biochemical failure (TTBF) | the time frame from the beginning date of radiation therapy (RT) to the date of PSA failure; | up to 8 years | 
| Time to progression (TTP) | time to progression (TTP), both local and distant defined as time from beginning date of RT to the date of progression of disease, both local and distant, or death whichever came first; | up to 8 years | 
| Overall Survival (OS) | overall survival, defined as the time from the start of treatment to the date of death from any cause, if data will be available, also cause specific survival will be calculated. | up to 8 years | 
| Quality of Life (QoL) | Treatment-related quality of life (QoL) according to the Functional Assessment of Cancer Therapy (FACT-Prostate) questionnaire; which consists of 39 items. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores. Higher scores represent better QoL. | before treatment, at 12 and 24 months of follow up | 
| Quality of urinary function | Urinary functions according to the International Prostate symptom Score (IPSS) questionnaire, which consists of 7 items. Each item is rated on a 0 to 5 score to produce a total I-PSS score with a range from 0 to 35 (asymptomatic to very symptomatic). | before treatment, at 3, 6, 12 and 24 months of follow up | 
| Quality of erectile function | Erectile functions according to International Index of Erectile Function (IEEF-5) questionnaire, which consists of 5 items. Each item is rated on a 1 to 5. High scores represent better erectile function. | before treatment, at 3, 6, 12 and 24 months of follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, organ-confined, external beam Radiotherapy, Image-guided tomotherapy