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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Adenocarcinoma; Radiotherapy; Complications; Tomotherapy
• Intervention / Treatment: Radiation: tomotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oriana Nanni, PhD; Phone Number: +390543739266; Email: oriana.nanni@irst.emr.it

Study Locations

• Italy
  • FC
    • Meldola, FC, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose external beam Radiotherapy; Image-guided tomotherapy	Radiation: tomotherapy; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Investigators: Study Chair: Sarah Pia Colangione, MD, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Prostate cancer; organ-confined; external beam Radiotherapy; Image-guided tomotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IRST185.06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No