Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation in Early Breast Cancer

Early-Stage Breast Carcinoma Clinical Trial

— HYPOSIB  

Official title:

Adjuvant Radiotherapy After Breast-conserving Surgery in Early Breast Cancer: Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02474641
• Other study ID #: ARO-2013-05, ZKS-121-001
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 16, 2015
• Est. completion date: March 31, 2028

Study information

• Verified date: March 2024
• Source: University Hospital Schleswig-Holstein
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypofractionation with simultaneous integrated boost has been investigated in a few trials and appears to be safe and feasible.

Investigators initiated this multicenter two-armed phase III prospective trial to analyse the non-inferiority of hypofractionation with simultaneous integrated boost in patients with early breast cancer in comparison to standard fractionation.

Description:

Control Arm:

Conventionaly fractionated radiotherapy of the breast 28 × 1.8 Gy = 50.4 Gy followed by a tumor bed boost sequentially 5 to 8 × 2.0 Gy = 10.0 Gy to 16.0 Gy, total dose 60.4 Gy to 66.4 Gy.

or Conventionaly fractionated radiotherapy of the breast 28 × 1.8 Gy = 50.4 Gy with simultaneous integrated boost to the tumor bed, total dose 28 × 0.3 Gy or 0.45 Gy= 8.4 Gy or 12,6 Gy, total dose 58,8 Gy to 63.0 Gy.

or Hypofractionated radiotherapy of the breast 16 × 2.66 Gy = 42.56 Gy followed by a tumor bed boost sequentially 5 to 8 × 2.0 Gy = 10.0 Gy to 16.0 Gy, total dose 52.56 Gy to 58.56 Gy.

Experimental Arm:

Hypofractionated radiotherapy of the breast 16 × 2.50 Gy with simultaneous integrated boost to the tumor bed, total dose within the boost volume 16 × 3.00 Gy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2324
• Est. completion date: March 31, 2028
• Est. primary completion date: January 8, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathologically confirmed breast cancer operated by breast conserving surgery with clear margins independently of further risk factors (positive or high-risk negative lymph node status, estrogen- or progesterone receptor status, Her-2/neu status uPA/PAI-1 criteria) and postoperative systemic therapy (chemotherapy, endocrine, antibody or bisphosphonate therapy were permitted when indicated)

• Indication to adjuvant radiotherapy including boost radiotherapy

• Clearly identified primary tumor region preferably by radiopaque clips

• Primary wound healing after breast conserving therapy without signs of infection

• Age = 18 years

• ECOG = 2 Performance Status

• Written informed consent

• Compliance regarding treatment appointments and toxicity

• Linguistic and cognitive ability to understand the questionnaires

Exclusion Criteria:

• Patients operated by mastectomy

• No indication for boost radiation (e.g. status after IORT)

• double sided breast cancer

• Resection margins positive for disease or insufficient identification of the boost volume

• Indication for radiotherapy of the regional lymph nodes

• History of prior breast or thoracic radiotherapy

• Extended postoperative seroma at the beginning of radiotherapy

• Previously administered radiotherapy not allowing the required dose

• Pregnant or lactating patients and woman of child bearing potential, who lacked effective contraception

• treatment history of other cancer or participation in another clinical trial testing radiotherapy or drugs within 4 weeks of the start of treatment.

• Patients with serious, uncontrolled, physical or cerebrovascular disorders(e.g. myocardial infarction within the last 12 months) or neurologiy or psychiatric disorders thought to adversly affect treatment compliance

Related Conditions & MeSH terms

• Breast Neoplasms
• Early-Stage Breast Carcinoma

Intervention

Radiation:
• Standard Radiation
Conventionally fractionated radiotherapy of the breast followed by a tumor bed boost sequentially or Conventionally fractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed or Hypofractionated radiotherapy of the breast followed by a tumor bed boost sequentially
• Hypofractionation with SIB
Hypofractionated radiotherapy of the breast with simultaneous integrated boost to the tumor bed

Locations

Country	Name	City	State
Germany	Gesundheitszentrum St.Marien Gmbh und Klinik für Strahlentherapie	Amberg
Germany	Medizinisches Versorgungszentrum Aue	Aue
Germany	Helios Kliniken Bad Saarow Klinik für Radioonkologie	Bad Saarow
Germany	HELIOS Klinikum Bad Saarow	Bad Saarow
Germany	Strahlentherapie Klinikum Bayreuth	Bayreuth
Germany	Ambulantes Gesundheitszentrum der Dr. med Maria Sternemann Charte -Universitätsmedizin Berlin	Berlin
Germany	Charite berlin (Virchow) Klinik für Strahlentherapie	Berlin
Germany	DRK Kliniken Berlin: Zentrum für Strahlentherapie MVZ pro patiente Westend	Berlin
Germany	HELIOS Klinikum Berlin-Buch, Strahlentherapeutische Klinik	Berlin
Germany	Medizinisches Versorgungs Zentrum Diagnostisch Therapeutisches Zentrum am Frankfurter Tor	Berlin
Germany	MZV am HELIOS Klinikum Emil von Behring	Berlin
Germany	Praxis für Radioonkologie und Strahlentherapie Berlin Südwest	Berlin
Germany	Strahlentherapie in Moabit /Praxis für Strahlentherapie	Berlin
Germany	Vivantes-Klinikum Berlin-Neukölln	Berlin
Germany	MVZ Chariete Vivantes Gmbh Strahlentherapie	Berlin ( Mitte)
Germany	Gemeinschaftspraxis und Belegabteilung für Strahlentherapie	Bocholt
Germany	Ambulanz Bremen GMBH MVZ RadioOnkologie	Bremen
Germany	Zentrum für Strahlentherapie undRadioonkologie	Bremen
Germany	Krankenhaus Buchholz Abteilung für Strahlentherapie	Buchholz
Germany	Strahlentherapie Coesfeld	Coesfeld
Germany	Radiologie Strahlentherapie-Zweigpraxis vom MVZ Passau	Deggendorf
Germany	Praxis für Strahlentherapie Krankenhaus Dresden-Friedrichsstadt	Dresden
Germany	Malteser MVZ Duisburg-Süd	Duisburg
Germany	Universitätsklinikum Düsseldorf Klinik und Poliklinik für Strahlentherapie und Radioologische Onkologie	Dusseldorf
Germany	Gemeinschaftspraxis für Strahlentherapie und Radioonkologie	Elmshorn
Germany	MVZ Strahlentherapie Klinikum Esslingen GmbH	Esslingen
Germany	Klinik für Strahlentherapie und Onkologie	Frankfurt/M
Germany	Klinikum Frankfurt (Oder)Klinikum für Strahlentherapie Radioonkologie	Frankfurt/Oder
Germany	Strahlentherapie am Klinikum Fürth	Fürth
Germany	Strahlentherapiezentrum- Escher-Lippe(STZELL) und die Katholischen Kliniken-Emscher	Gelsenkirchen
Germany	Justus-Liebig Universität Gießen Strahlentherapie	Gießen
Germany	Praxis für Strahlentherapie Goch	Goch
Germany	Brustzentrum ALB FILS Kliniken GMBH	Göppingen
Germany	Ambulanzzentrum des UKE GmbH Bereich der Strahlentherapie	Hamburg
Germany	Radiologische Ambulanz Fachärzte für Radiologie,Nuklearmedizin und Strahlentherapie	Hamburg
Germany	Strahlenzentrum Hamburg	Hamburg
Germany	Dr.med Jürgen Heide Facharzt für Strahlentherapie	Hamburg Harburg
Germany	GSR Hameln	Hameln
Germany	Gemeinschaftspraxis für Strahlentherapie und Radioonkologie / Hannover/Hildesheim/Hameln	Hannover
Germany	GSR Hannover Siloa	Hannover
Germany	Gemeinschaftspraxis für Strahlentherapie Hildesheim/Goslar	Hildesheim
Germany	Gemeinschaftspraxis für Strahlentherapie und Radioonkologie(GSR)	Hildesheim
Germany	Gemeinschaftspraxis für Strahlentherapie/Hildesheim/Goslar	Hildesheim
Germany	Strahlentherapie Hof	Hof
Germany	MVZ St. Vincent-Kliniken gAG	Karlsruhe
Germany	Praxis für Strahlentherapie am Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitätsklinikum Leibzig	Leipzig
Germany	Klinikum für Strahlentherapie - Klinikum Lippe	Lemgo
Germany	Klinikum Ludwigsburg Klinik für Radioonkologie	Ludwigsburg
Germany	Klinikum Lüneburg, Klinik für Strahlentherapie und Radioonkologie	Lüneburg
Germany	MVZ Prof.Dr.Uhlenbrock und Partner Strahlentherapie Lünen	Lünen
Germany	Klinik und Poliklinik für Radioonkologie und Strahlentherapie Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Praxis für Strahlentherapie Mannheim	Mannheim
Germany	Universitätsklinikum Marburg Strahlentherapie und Radioonkologie	Marburg
Germany	Brustzentrum Helios Klinikum	Meiningen
Germany	Kliniken Maria Hilf Gmbh Klinik für Strahlentherapie	Monchengladbach
Germany	Klinikum rechts der Isar	Muenchen
Germany	Klinik für Strahlentherapie- Radioonkologie	Münster
Germany	Praxis für Strahlentherapie und Radioonkologie am Clemenshospital	Münster
Germany	Strahlentherapie Neckarsulm	Neckarsulm
Germany	Dietrich Bonhoeffer Klinikum Neubrandenburg	Neubrandenburg
Germany	Praxis für Strahlentherapie Im Städtischen Klinikum Neunkirchen	Neunkirchen
Germany	Klinik für Strahlentherapie und Radioonkologie Pius-Hospital Oldenburg	Oldenburg
Germany	Zentrum für Strahlentherapie Rheine-Osnabrück	Osnabrück
Germany	MVZ Radio-LOG Schie in Altötting	Passau
Germany	Visiorad - Bereich Strahlentherapie	Pinneberg
Germany	Klinikum für Radioonkologie Klinikum Ernst von Bergmann	Potsdam
Germany	Krankenhaus Barmherzige Brüder Regensburg Medizinisches Versorgungszentrum	Regensburg
Germany	Überörtliche Gemeinschaftspraxis/Fachärzte für Strahlentherapie	Rheine
Germany	Kreiskliniken Esslingen Paracelsus Krankenhaus Ruit	Ruit
Germany	CaritasKlinikum Saarbrücken	Saarbrucken
Germany	XCare Praxis für Strahlentherapie	Saarlouis
Germany	MVZ Leopoldina	Schweinfurt
Germany	MVZ Leopoldina Strahlentherapie	Schweinfurt
Germany	Helios kliniken Schwerin GMBH	Schwerin
Germany	Johanniter Zentren für medizinische Versorgung in der Altmark GMBH	Stendal
Germany	Johanniter Zentrum für Medizinische Versorgung	Stendal
Germany	MVZ Klinikum Straubing GMBH Strahlentherapie	Straubing
Germany	MVZ-Uniklinik Tübingen gGmbH	Stuttgart
Germany	Praxis für Strahlentherapie Trier Ehrang	Trier
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Klinik für Strahlentherapie und Radioonkologie Universitätsklinikum Ulm	Ulm
Germany	Klinik für Strahlentherapie und Radioonkologie Schwarzwald-Baar -Klinikum	Villingen-Schwenningen
Germany	Praxis für Strahlentherapie und Radioonkologie am Krankenhaus Weilheim	Weilheim
Germany	Medizinisches Versorgungszentrum Wolfsburg GmbH	Wolfsberg
Germany	Universitätsklinikum Würzburg Klinik und Poliklinik für Strahlentherapie	Würzburg
Germany	Heinrich-Braun-Klinikum Zwickau	Zwickau

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Schleswig-Holstein	University of Luebeck

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Krug D, Vonthein R, Schreiber A, Boicev AD, Zimmer J, Laubach R, Weidner N, Dinges S, Hipp M, Schneider R, Weinstrauch E, Martin T, Horner-Rieber J, Olbrich D, Illen A, Hessler N, Konig IR, Dellas K, Dunst J. Impact of guideline changes on adoption of hypofractionation and breast cancer patient characteristics in the randomized controlled HYPOSIB trial. Strahlenther Onkol. 2021 Sep;197(9):802-811. doi: 10.1007/s00066-020-01730-9. Epub 2020 Dec 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	any local or regional recurrence or distant metastasis or death	3 to 6 years
Secondary	Time to occurence of local recurrence	ipsilateral in-breast recurrence	3 to 6 years
Secondary	Overall survival	death	3 to 6 years
Secondary	Safety and side effects (Number of Patients with Adverse Events)	Number of Patients with Adverse Events	3 to 6 years
Secondary	Acute and chronic toxicity (NCI-CTCAE)	All dimensions of NCI-CTCAE	1 day, 7 days, end of radiation (last day of radiation and closing visite), 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months, 48 months, 54 months, 60 months, 66 months, 72 months
Secondary	Cosmetic results (NCI-CTCAE)	NCI-CTCAE	1 day, end of radiation (last day of radiation and closing visite), 3 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months