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

• ClinicalTrials.gov Identifier: NCT03553212
• Recruitment Status: Recruiting
• First Posted: June 12, 2018
• Last Update Posted: November 9, 2018
• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Information provided by (Responsible Party): Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Adenocarcinoma; Radiotherapy; Complications; Tomotherapy	Radiation: tomotherapy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 31 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Feasibility trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Twice High Dose External Beam Radiotherapy by Image-guided Tomotherapy for Organ-confined Prostate Cancer Treatment Emulating HDR Brachytherapy: Single Institution Feasibility Study
• Actual Study Start Date: October 30, 2018
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. occurrence of Grade ≥3 early GU toxicity [ Time Frame: within 3 months after end of Radiotherapy ]
   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
2. occurrence of Grade ≥3 early GI toxicity [ Time Frame: within 3 months after end of Radiotherapy ]
   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

Secondary Outcome Measures :

1. Occurrence of Grade ≥3 Late GU toxicity [ Time Frame: more than 6 months after end of Radiotherapy ]
   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
2. Evaluation of Prostate Antigen Serum (PSA) failure [ Time Frame: up to 8 years ]
   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.
3. Time to biochemical failure (TTBF) [ Time Frame: up to 8 years ]
   the time frame from the beginning date of radiation therapy (RT) to the date of PSA failure;
4. Time to progression (TTP) [ Time Frame: up to 8 years ]
   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;
5. Overall Survival (OS) [ Time Frame: up to 8 years ]
   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.
6. Quality of Life (QoL) [ Time Frame: before treatment, at 12 and 24 months of follow up ]
   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.
7. Quality of urinary function [ Time Frame: before treatment, at 3, 6, 12 and 24 months of follow up ]
   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).
8. Quality of erectile function [ Time Frame: before treatment, at 3, 6, 12 and 24 months of follow up ]
   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.

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Oriana Nanni, PhD; +390543739266; oriana.nanni@irst.emr.it

Locations

Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); Recruiting

Meldola, FC, Italy, 47014

Contact: Sarah Colangione, md +390543739170 sarah.colangione@irst.emr.it

Principal Investigator: Sarah Colangione, MD

Sub-Investigator: Antonino Romeo, MD

Sponsors and Collaborators

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)

More Information

• Responsible Party: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• ClinicalTrials.gov Identifier: NCT03553212 History of Changes
• Other Study ID Numbers: IRST185.06
• First Posted: June 12, 2018
• Last Update Posted: November 9, 2018
• Last Verified: November 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori:

Prostate cancer; organ-confined; external beam Radiotherapy; Image-guided tomotherapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Adenocarcinoma; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type