Longitudinal Evaluation of Intestinal, Haematological and Urinary Toxicity From Pelvic Irradiation for Prostate Cancer (IHU-WPRT-TOX)

January 4, 2023 updated by: Cesare Cozzarini, IRCCS San Raffaele

The prophylactic irradiation of pelvic lymph-nodes by means of Whole-Pelvis Radiotherapy (WPRT) in the treatment of prostate cancer (PCa) is aimed at the timely eradication of microscopic lymph-nodal metastases. Nevertheless, even though delivered by means of modern Intensity-Modulated Radiotherapy (IMRT) techniques, WPRT may result in intestinal, hematologic and urinary toxicity (IT, HT, UT, respectively) severely affecting patients' daily health-related quality-of-life (HRQoL) within the so-called and inadequately investigated Pelvic Radiation Disease.

The aim of this study is to develop sophisticated predictive models of IMRT-WPRT induced patient-reported HT, IT and UT in PCa. The possible correlation between several clinical factors and radiation doses received by various pelvic structures (i.e. pelvic bones subvolumes, intestinal loops, sigmoid, rectum and bladder) and risk and severity of patient-reported IT, UT and HT will be analyzed and robust multi-variable models will be developed and internally validated. A secondary end-point will be the identification of specific symptoms affecting patients' HRQoL during irradiation and in the long term, overall and in different therapeutic settings (radical, adjuvant and salvage). Lastly, possible correlation between HT and UT/IT will be investigated.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

Experimental Design:

Hypothesis. Dose-volume histograms (DVHs) of bowel, sigmoid colon and rectum are expected to be predictive of IT prospectively self-assessed by patients by means of IBDQ (Inflammatory Bowel Disease Questionnaire). Similarly, DVHs of pelvic bony subvolumes (lumbar-sacral, iliac and the lower pelvis) should predict HT, while DVHs and dose-surface histograms (DSHs) of the bladder are expected to be predictive of UT self-assessed by patients by means of IPSS (International Prostate Symptoms Score) and ICIQ-SF (International Consultation on Incontinence Questionnaire- short form) questionnaires. Moreover, some specific urinary and intestinal-rectal symptoms are expected to lead to impairment in emotional, social and systemic domains, as assessed by the IBDQ questionnaire, more than others, with several possible "clusters" of symptoms prevailing in different treatment settings. Finally, the intestinal, urinary and hematologic toxicity profile of WPRT IMRT could emerge to be extremely different in patients treated with radical (RAD), adjuvant (ADV) or salvage (SALV) intent.

Task1. The principal aim of the project is to develop sophisticated quantitative predictive models of IT, UT and HT (without the confounding bias of chemotherapy) from WPRT IMRT in both radical and postoperative treatment of localized PCa. The possible correlation between the radiation doses received by different pelvic structures and different toxicities will be analyzed.

Task2. To try to individuate the intestinal/rectal and urinary symptoms most negatively affecting the Emotional, Social and Systemic patient domains, with the ultimate objective of "focusing" the quantitative predictive models including both clinical and physico-dosimetric parameters only upon these main symptoms. This approach could theoretically permit the creation of a "shortened and radiotherapy adapted" version of the IBDQ questionnaire.

Task3. A thorough assessment of the different self-assessed toxicity profiles to be expected in patients treated with RAD, ADV or SALV intent will be carried out, with the ultimate aim of accumulating a set of extremely detailed information to be provided to patients in order to offer them appropriate counselling after the initial diagnosis of PCa with regard to the choice between radiotherapy vs surgery. In those selecting the latter and in the presence of risk factors at prostatectomy suggesting a possible role for postoperative radiotherapy, the ultimate objective would be that of assisting patients in the always extremely problematic choice between immediate adjuvant and timely, postponed, salvage irradiation in the case of biochemical recurrence.

Task4. Secondary end-points: to search for a possible correlation between HT and IT/UT.

Throughout the treatment period, patients will be seen every 2 weeks for toxicity monitoring. Subsequently, a follow-up visit will be performed at 3 months from the end of treatment, and every six months thereafter, up to 5 years.

Intestinal and urinary toxicities, including urinary incontinence, will be self-assessed by patients by means of the Italian validated version of the IBDQ, IPSS and ICIQ-SF questionnaires: at baseline (no more than 30 days before RT start), at radiotherapy mid-point and end, at 3, 6,12, 18, 24, 30, 36, 42, 48, 54 and 60 months from radiotherapy conclusion.

A blood sample for white blood cells (WBC), with absolute neutrophil and lymphocyte counts (ANC and ALC, respectively), red blood cells (RBC) and platelets (PLT) counts will be collected at the same time intervals. In addition to the self-reported assessment of rectal/bowel and urinary symptoms during and after radiotherapy, an evaluation of acute and late IT and UT will be performed by the medical staff for possible future comparison between its subjective and objective measurement. IT, HT and UT will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Study Type

Observational

Enrollment (Anticipated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

Patients with histologically proven adenocarcinoma of the prostate, candidate to radical or postoperative (both adjuvant and salvage) radiotherapy including prophylactic irradiation of the pelvic lymph-nodal area. The indication for WPRT will be at the discretion of the referring Radiation Oncologist.

Description

Inclusion Criteria:

  • Patients with with an ECOG PS 0-1
  • Patients with histologically proven adenocarcinoma of the prostate
  • WPRT can be delivered with both static and rotational IMRT techniques such as volumetric modulated arc therapy (VMAT) or Tomotherapy
  • Both conventionally (1.8-2 Gy/fraction) and moderately hypo-fractionated (≤ 2.7 Gy/fraction) regimens with simultaneous integrated boost (SIB) approach are allowed; in any case the daily dose delivered to the pelvic nodes should be in the range of 1.8-2.0 Gy/fr

Exclusion Criteria:

  • Patients older than 80 years at the time of enrollment
  • Missing written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
1
To date, around 700 patients, who were treated with Radiotherapy for Prostate Cancer, have been enrolled. 34% of them underwent radiotherapy with radical intent, whereas the others were post-prostatectomy patients (29% adjuvant, 37% salvage). Various techniques of irradiation were used (1% 3DCRT, 6% SF-IMRT, 52% VMAT, 41% Tomotherapy) in conventional (42%, 1.7-2.0 Gy/fr.) and hypofractionated (58%, 2.1-2.7 Gy/fr.) settings. EQD2(alpha/beta=3) to prescribed PTV ranged between 64 and 93 Gy. Limph nodes were treated in the 98% of cases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematologic toxicity
Time Frame: 5 years
if any, acute (<within 90 days from radiotherapy completion) and late (>90 days from radiotherapy completion) Grade 1, Grade 2 and Grade 3-4 leukopenia, neutropenia, lymphopenia, erythropenia, anemia, thrombocytopenia and clinico-dosimetric factors predicting them;
5 years
Intestinal toxicity
Time Frame: 5 years
a worsening of 2 points or more with respect to baseline of the 10 IBDQ items investigating the Bowel Domain (items # 1, 5, 9, 13, 17, 20, 22, 24, 26 and 29, frequency of bowel movements, liquid defecation, abdominal cramps, abdominal pain, gas passage, abdominal bloating, rectal bleeding, urge to go to bathroom even if empty intestine, accidental soiling and nausea/feeling sick, respectively) and of the three cumulative items evaluating the impact of Bowel Symptoms on the Emotional, Social and Systemic Domains.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Collaborators

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Regina Elena Cancer Institute
Arcispedale Santa Maria Nuova-IRCCS
Associazione Italiana per la Ricerca sul Cancro
Candiolo Cancer Institute - IRCCS
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
Cliniche Humanitas Gavazzeni
Azienda Sanitaria Locale di Biella
Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy
Azienda Sanitaria dell'Alto Adige
Centro AKTIS Diagnostica e Terapia
Azienda Sanitaria Locale To4
Azienda U.S.L. della Valle d'Aosta
IRCCS Centro di Riferimento Oncologico della Basilicata

Investigators

  • Study Chair: Cesare Cozzarini, MD, IRCCS San Raffaele Scientific Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

December 1, 2021

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

June 8, 2016

First Submitted That Met QC Criteria

June 15, 2016

First Posted (Estimate)

June 16, 2016

Study Record Updates

Last Update Posted (Actual)

January 6, 2023

Last Update Submitted That Met QC Criteria

January 4, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRCCS San Raffaele

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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