Intra-Operative Electron Boost and Hypofractionated Whole-Breast Irradiation During Breast-conserving Treatment (BCT) (HIOB)

December 31, 2022 updated by: Gerd Fastner, Paracelsus Medical University

Hypofractionated Whole-Breast Irradiation Preceded by Intra-Operative Radiotherapy With Electrons as Anticipated Boost HIOB A New Option in Breast-Conserving Treatment for Operated Breast Cancer Stages I and II

Title:

HIOB - Hypofractionated Whole-Breast Irradiation preceded by Intraoperative Radiotherapy with Electrons as anticipated Boost ISIORT- 01

HIOB is defined as hypofractionated WBRT (40,5 Gy in 2,7 Gy per fraction) preceded by an Intraoperative Boost to the tumor bed ( 90 % reference dose of 10 Gy, 11,1 Gy Dmax IOERT).

Primary endpoint is the proof of superiority of a new treatment regimen.

The HIOB study concept is supposed to test the hypothesis whether such a combined schedule is superior (or iso-effective) towards "standard" RT in terms of local control and cosmetic outcome.

In the vast majority of all publications, annual and 5 year in-breast recurrence rates following BCT showed a clear dependency on patient age within the following boundaries (primary references):

Age > 50: Bartelink (standard): 0,7% (annual) 3,5% (5y) START B (best): 0,4 %(annual) 2,0% (5y)

Age 41-50: Bartelink (standard) 1,2% (annual) 6,0% (5y) Whelan (best) 0,72%(annual) 3,6% (5y)

Age ≥ 35-40 Bartelink (standard) 2% (annual) 10% (5y) Whelan (best) 0,72% (annual) 3,6% (5y)

long these three different age groups, benchmarking will be performed against the best published results following 'Golden Standard'RT, usually defined as conventionally fractionated WBRT with 50 Gy (25 x2) plus external tumor bed boost with 10-16 Gy electrons (5-8x2Gy).

Superiority is defined as going below the lower limit of the estimated 5 year local recurrence rate within the respective age group Inferiority is defined as crossing the respective upper limit .

Secondary endpoint:

Disease free survival

Tertiary endpoint: toxicity assessment (acute and late) including long term cosmetic evaluation

Study design and statistics:

  • Prospective multicenter single-armed
  • Sequential probability ratio test (SPRT)
  • Separate analysis within three different age groups

Estimated Accrual time: strongly dependent on recruitment per year within the respective age group . Due to the statistical estimation of Szenario A and B the study will close after max. Time-period of 10 years in case of A or 6,4 years in case of B..

Principal investigators and study coordinators:

UC of Radiotherapy and Radio-Oncology UC of Special Gynecology and Breast Cancer Center Landeskrankenhaus Salzburg, Paracelsus University Clinics

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study population:

See Points 4.1 und 4.2 Inclusion/Exclusion criteria of the entire protocol

Operation:

  • Lumpectomy / segmentectomy / tumorectomy with sufficient safety margins (see above). Lymph node assessment must follow a sentinel node concept.
  • Perioperative antibiotic prophylaxis is mandatory
  • After IORT, radio-opaque clips have to be fixed at the tumor bed.

Histology: R0-Resection is mandatory

Chemotherapy:

neoadjuvant:allowed adjuvant: allowed.

There are no limitations towards special chemotherapeutic schemes and schedules.

Radiotherapy:

IOERT

  • IOERT is performed on mobile or fixed linacs
  • Reference dose: 11 Gy specified as maximum dose, with a minimum target volume dose of 90% encompassing the PTV (i.e. 10 Gy).

WBRT

  • must start within day 36- 56 postoperatively (week 6 - 8 p.o.) in case of adjuvant hormonal treatment (or no further tumor specific medication)
  • In case of adjuvant chemotherapy, a time - gap between IOERT and WBRT up to 9 months is allowed.
  • Single reference dose per fraction: 2,7 Gy (ICRU)
  • Number of fractions: 15, Number of fractions per week: 5
  • Total WBRT dose: 40,5 Gy

RT of regional lymphatics: exclusion criterion

Diagnostics of Local recurrence:

  • yearly mammographies,
  • optional breast sonography, MRI
  • LR has to be histologically confirmed

Follow-up screening for detection of metastases (minimum requirements):

  • Chest X-Ray, optional
  • abdominal sonography, optional
  • lab tests incl. tumor markers, optional

Assessment of acute toxicity of WBRT according to CTC-toxicity Scoring-systems:

Assessment of late toxicity according to LENT-SOMA scoring-systems

Assessment of cosmetic outcome according to 5-point- Scoring System (vanLimbergen) starting before WBRT, including photo documentation in standardized positions

Study Type

Interventional

Enrollment (Actual)

1464

Phase

  • Not Applicable

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

  • Austria
      • Salzburg, Austria, 5020
        • Paracelsus private university; University Clinic of Radio-Oncology

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

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histological proven invasive breast carcinoma
  • Age: ≥ 35 years
  • Tumor stage T1-2
  • nodal status: N0-1
  • Freedom of surgical margins: R0 (both invasive and in situ component), that means no ink on tumors (invasive or in situ) (ago-online.de) .
  • Also multifocal disease within the same quadrant with a maximum distance of < 5 cm
  • all grades G1-G3
  • Hormonal receptor and Her-2 status: no limitations
  • Informed and undersigned consent

Exclusion Criteria:

  • In-situ Carcinoma without invasive component
  • Age < 35
  • Tumor stage T3,4
  • Nodal status >N1
  • if irradiation of regional lymphatics is required
  • R1
  • Re-excision after IOERT
  • Immediately secondary mastectomy (not due to recurrence).
  • Multicentricity according to international definition: > 5 cm distance to each other
  • previous radiotherapy to the involved breast
  • Karnofsky Index < 70%
  • Mixed connective tissue diseases including rheumatoid Polyarthritis, Thrombangitis obliterans
  • Chronic pre-existent lung disease (Lung fibrosis, Pneumokoniosis, late-type Allergies like Farmer lung; Asthma bronchiale, severe Emphysema, COPD III *)
  • Cardiac Co-Morbidity: clinically positive coronary vessel disease, St.p. myocardial infarction, pacemakers and/or defibrillators)
  • Distant metastases
  • breast size (PTV) > 2500 ml
  • missing written consent
  • observed pregnancy

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

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IOERT followed by hypofractionated WBRT
HIOB: IOERT of 11.1 Gy followed by WBRT with 15 times 2.7 Gy per fraction.
Radiation: HIOB

IOERT single shot as a boost followed by hypofractionated WBRT (HIOB)

  • IOERT is performed on mobile or fixed linacs
  • Reference dose: 11 Gy specified as maximum dose, with a minimum target volume dose of 90% encompassing the PTV (i.e. 10 Gy).

WBRT

  • must start within day 36- 56 postoperatively (week 6 - 8 p.o.) in case of adjuvant hormonal treatment (or no further tumor specific medication)
  • In case of adjuvant chemotherapy, a time - gap between IOERT and WBRT up to 9 months is allowed.
  • Single reference dose per fraction: 2,7 Gy (ICRU)
  • Number of fractions: 15, Number of fractions per week: 5
  • Total WBRT dose: 40,5 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5 year local recurrence rate: Sequential Probability Ratio Test
Time Frame: 10 years
Sequential Probability Ratio Test
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems
Time Frame: 10 years
CTC-toxicity Scoring-System;LENT-SOMA scoring-systems
10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cosmesis
Time Frame: 10 years
van Limbergen Scoring System
10 years

Collaborators and Investigators

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

Sponsor

Paracelsus Medical University

Collaborators

Heinrich-Heine University, Duesseldorf
Poznan University of Medical Sciences
University Hospital of Ferrara
Fondazione Salvatore Maugeri
Philipps University Marburg Medical Center
Avera McKennan Hospital & University Health Center
IRCCS Cancer Referral Center of Basilicata
Azienda Ospedaliero Universitaria Maggiore della Carita
Istituti Tumori Giovanni Paolo II
Azienda Ospedaliero, Universitaria Ospedali Riuniti
San Filippo Neri General Hospital
LKH Klagenfurt
St. Luke's Hospital ,Cedar Rapids, US
A.O.U. San Giovanni Battista di Torino, Italy
St. Elisabeth-Hospital Köln-Hohenlind, Germany
S.C. Radiotherapia Aziendale Umbria, Italy
Marien Hospital Düsseldorf

Investigators

  • Principal Investigator: Gerd Fastner, Assoc.Prof., Dep. of Radiotherapy and Radio-Oncology, Paracelsus Medical University Salzburg

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 (Actual)

January 1, 2011

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

April 26, 2011

First Submitted That Met QC Criteria

April 27, 2011

First Posted (Estimate)

April 28, 2011

Study Record Updates

Last Update Posted (Estimate)

January 4, 2023

Last Update Submitted That Met QC Criteria

December 31, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIORT - 01
  • ISIORT 01 (Other Identifier: ISIORT)

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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