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Local Neoplasm RecurrenceHIOBNCT01343459

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

A study testing HIOB in people with Local Neoplasm Recurrence and Toxicity, run by Paracelsus Medical University at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 35 years and older, women only
Conditions the study is for
Local Neoplasm Recurrence, Toxicity
What is being tested?
HIOB
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,464 participants
Where
1 siteAustria
Study dates
Jan 2011to 31 Dec 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • all grades G1-G3
  • Hormonal receptor and Her-2 status: no limitations
  • Informed and undersigned consent

Who cannot join

  • In-situ Carcinoma without invasive component
  • Age < 35
  • Tumor stage T3,4
  • Nodal status >N1
  • if irradiation of regional lymphatics is required
  • R1
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Austria1 site
  • Paracelsus private university; University Clinic of Radio-Oncology

    Salzburg, 5020

Other trials in Austria

About this study

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

Title:

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

Read more

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

Read the 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

Being tested
HIOB
Keywords
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
Medical subject headings
Neoplasm Recurrence, Local

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HIOBRadiation

    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
Study groups in NCT01343459
Study groupRoleWhat they receive
IOERT followed by hypofractionated WBRTExperimentalHIOB: IOERT of 11.1 Gy followed by WBRT with 15 times 2.7 Gy per fraction.
Receives: Radiation: HIOB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 5 year local recurrence rate: Sequential Probability Ratio Test

    Sequential Probability Ratio Test

    Measured: 10 years

Secondary outcomes (1)
  1. Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems

    CTC-toxicity Scoring-System;LENT-SOMA scoring-systems

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2011 (estimated)
  2. Study startJan 2011
  3. Primary completion31 Dec 2022
  4. Study completion31 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1,464 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01343459
Sponsor's protocol ID
ISIORT - 01
Other IDs
ISIORT 01
Acronym
HIOB
Status last verified
Dec 2022
First submitted
26 Apr 2011
Last updated
4 Jan 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I, Fourquet A, Borger J, Jager J, Hoogenraad W, Collette L, Pierart M; European Organization for Research and Treatment of Cancer Radiotherapy and Breast Cancer Groups. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001 Nov 8;345(19):1378-87. doi: 10.1056/NEJMoa010874.

    PubMed 11794170
  • START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107. doi: 10.1016/S0140-6736(08)60348-7. Epub 2008 Mar 19.

    PubMed 18355913
  • Whelan TJ, Kim DH, Sussman J. Clinical experience using hypofractionated radiation schedules in breast cancer. Semin Radiat Oncol. 2008 Oct;18(4):257-64. doi: 10.1016/j.semradonc.2008.04.008.

    PubMed 18725113
  • Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20. doi: 10.1056/NEJMoa0906260.

    PubMed 20147717
  • Ivaldi GB, Leonardi MC, Orecchia R, Zerini D, Morra A, Galimberti V, Gatti G, Luini A, Veronesi P, Ciocca M, Sangalli C, Fodor C, Veronesi U. Preliminary results of electron intraoperative therapy boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):485-93. doi: 10.1016/j.ijrobp.2007.12.038. Epub 2008 Apr 11.

    PubMed 18407434
  • START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008 Apr;9(4):331-41. doi: 10.1016/S1470-2045(08)70077-9. Epub 2008 Mar 19.

    PubMed 18356109
  • Owen JR, Ashton A, Bliss JM, Homewood J, Harper C, Hanson J, Haviland J, Bentzen SM, Yarnold JR. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. Lancet Oncol. 2006 Jun;7(6):467-71. doi: 10.1016/S1470-2045(06)70699-4.

    PubMed 16750496
  • Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson J, Haviland J, Bentzen S, Owen R. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol. 2005 Apr;75(1):9-17. doi: 10.1016/j.radonc.2005.01.005. Epub 2005 Mar 16.

    PubMed 15878095
  • Reitsamer R, Sedlmayer F, Kopp M, Kametriser G, Menzel C, Deutschmann H, Nairz O, Hitzl W, Peintinger F. The Salzburg concept of intraoperative radiotherapy for breast cancer: results and considerations. Int J Cancer. 2006 Jun 1;118(11):2882-7. doi: 10.1002/ijc.21727.

    PubMed 16381011
  • Reitsamer R, Peintinger F, Sedlmayer F, Kopp M, Menzel C, Cimpoca W, Glueck S, Rahim H, Kopp P, Deutschmann H, Merz F, Brandis M, Kogelnik H. Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients. Eur J Cancer. 2002 Aug;38(12):1607-10. doi: 10.1016/s0959-8049(02)00116-8.

    PubMed 12142049
  • Sedlmayer F, Fastner G, Merz F, Deutschmann H, Reitsamer R, Menzel C, Ciabattoni A, Petrucci A, Hager E, Willich N, Orecchia R, Valentini V; International Society of Intraoperative Radiotherapy. IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis. Strahlenther Onkol. 2007 Dec;183 Spec No 2:32-4. doi: 10.1007/s00066-007-2013-6. No abstract available.

    PubMed 18167006
  • Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, Lada B, Lukka H, Perera F, Fyles A, Laukkanen E, Gulavita S, Benk V, Szechtman B. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst. 2002 Aug 7;94(15):1143-50. doi: 10.1093/jnci/94.15.1143.

    PubMed 12165639

Questions about this trial

What is this clinical trial studying?

A study testing HIOB in people with Local Neoplasm Recurrence and Toxicity, run by Paracelsus Medical University at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

5 year local recurrence rate: Sequential Probability Ratio Test (time frame: 10 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01343459, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.

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