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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2011 by Paracelsus Medical University
Sponsor:
Collaborators:
LKH Klagenfurt
Poznan University of Medical Sciences
San Filippo Neri General Hospital
RWTH Aachen University
Information provided by:
Paracelsus Medical University
ClinicalTrials.gov Identifier:
NCT01343459
First received: April 26, 2011
Last updated: April 27, 2011
Last verified: March 2011
  Purpose

Title:

HIOB - Hypofractionated Whole-Breast Irradiation preceded by Intra-Operative 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 Intra-Operative 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 multi-center 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


Condition Intervention Phase
Local Neoplasm Recurrence
Toxicity
Radiation: HIOB
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Paracelsus Medical University:

Primary Outcome Measures:
  • 5 year local recurrence rate: Sequential Probability Ratio Test [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: January 2011
Estimated Study Completion Date: May 2021
Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypofractionated WBRT with IOERT Boost Radiation: HIOB

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 6 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

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 tumorbed.

Chemotherapy:

neoadjuvant: not 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 6 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,
  • abdominal sonography,
  • lab tests incl. tumor markers.

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 photodocumentation in standardized positions

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological proven invasive breast carcinoma
  • Age: ≥ 35 years
  • Tumor stage T1-2
  • nodal status: N0-1
  • Freedom of surgical margins: R0; ≥ 2 mm (both invasive and in situ component). Exception: In dorsal direction it could be below 2 mm margin if the pectoralis fascia was additional removed; also in ventral direction it could be < 2mm if skin was a part of resection and second resection is not possible.
  • 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
  • surgical margins/ histological clearance < 2mm
  • 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 (Lungfibrosis, 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)
  • neoadjuvant CT
  • Distant metastases
  • breast size (PTV) -≥ 1800 ml
  • missing written consent
  • observed pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01343459

Contacts
Contact: Felix Sedlmayer, Prof. MD 0043/662/4482/3915 f.sedlmayer@salk.at
Contact: Gerd Fastner, MD 0043/662/4482/58918 g.fastner@salk.at

Locations
Austria
Paracelsus private university; University Clinic of Radio-Oncology Recruiting
Salzburg, Austria, 5020
Contact: Felix Sedlmayer, chairman Prof. MD    0043/662/4482/3915    f.sedlmayer@salk.at   
Contact: Gerd Fastner, MD    0043/662/4482/58918    g.fastner@salk.at   
Principal Investigator: Felix Sedlmayer, chairman Prof. MD         
Sponsors and Collaborators
Paracelsus Medical University
LKH Klagenfurt
Poznan University of Medical Sciences
San Filippo Neri General Hospital
RWTH Aachen University
Investigators
Principal Investigator: Felix Sedlmayer, Prof. MD Paracelsus private university; University Clinic of Radio-Oncology, Müllnerhaupstraße 48 5020 Salzburg/Austria/Europe
  More Information

Publications:

Responsible Party: Sedlmayer, Paracelsus medical university
ClinicalTrials.gov Identifier: NCT01343459     History of Changes
Other Study ID Numbers: ISIORT - 01, ISIORT 01
Study First Received: April 26, 2011
Last Updated: April 27, 2011
Health Authority: Austria: Ethikkommission

Keywords provided by Paracelsus Medical University:
Hypofractionated Whole breast irradiation
Hypofractionated Whole breast irradiation long term results
Breast conserving therapy
IORT with electrons in breast cancer
IOERT as anticipated Boost
IOERT and hypofractionated whole breast irradiation

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasm Recurrence, Local
Recurrence
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Disease Attributes

ClinicalTrials.gov processed this record on August 19, 2014