Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast

Carcinoma, Ductal, Breast Clinical Trial

— DCIS  

Official title:

A Randomised Phase III Study of Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00470236
• Other study ID #: TROG 07.01
• Secondary ID: NHMRC 454390BIG
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 2007
• Est. completion date: June 2024

Study information

• Verified date: March 2023
• Source: Trans Tasman Radiation Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypotheses: 1. The addition of tumour bed boost after BCS in women with non-low risk DCIS reduces the risk of local recurrence (invasive or intraductal recurrence in the ipsilateral breast). 2. The risk of local recurrence in the shorter fractionation arm is not worse than that for the standard fractionation arm. 3. A molecular signature predictive of invasive recurrence of DCIS will be detectable and the molecular signature may eventually have clinical utility for therapy individualization. Overall Objectives: 1. To improve the outcome of women with non-low risk DCIS treated with breast conserving therapy. 2. To individualize treatment selection for women with DCIS to achieve long term disease control with minimal toxicity.

Description:

Specific objectives: 1. To evaluate time to local recurrence in women with DCIS treated with breast conserving surgery followed by: - whole breast RT alone versus whole breast RT plus tumour bed boost; - RT using the standard fractionation schedule versus the shorter schedule. 2. To evaluate time to disease recurrence and overall survival in women with DCIS treated with breast conserving surgery followed by: - whole breast RT alone versus whole breast RT plus tumour bed boost; - RT using the standard fractionation schedule versus the shorter schedule. 3. To compare the toxicity of: - whole breast RT alone versus whole breast RT plus tumour bed boost; - RT using the standard fractionation schedule versus the shorter schedule. 4. To compare the cosmetic outcome of: - whole breast RT alone versus whole breast RT plus tumour bed boost; - RT using the standard fractionation schedule versus the shorter schedule. 5. To identify a molecular signature predictive of invasive recurrence of DCIS to facilitate therapy individualization. 6. To assess inter-relationship of biomarkers and relationship between biomarker expression and specific histopathologic features of DCIS. 7. To evaluate the quality of life of women treated with: - whole breast RT alone versus whole breast RT plus tumour bed boost; - RT using the standard fractionation schedule versus the shorter schedule.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1608
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients must fulfill all of the following criteria for admission to study:

• Women = 18 years.
• Histologically proven DCIS of the breast without an invasive component.
• Bilateral mammograms performed within 6 months prior to randomization.
• Clinically node-negative.
• Treated by breast conserving surgery (primary excision or re-excision) with complete microscopic excision and clear radial margins of =1 mm* (*Patients with superficial or deep resection margin of <1 mm are eligible if surgery has removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia).
• Women who are at high risk of local recurrence due to:
• Age < 50 years; OR
• Age = 50 years plus at least one of the following:
• Symptomatic presentation
• Palpable tumour
• Multifocal disease
• Microscopic tumour size = 1.5 cm in maximum dimension
• Intermediate or high nuclear grade
• Central necrosis
• Comedo histology
• Radial* surgical resection margin < 10 mm. (*Patients with superficial or deep resection margin of < 10 mm are eligible if surgery has not removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia.)
• Assessed by surgeon and radiation oncologist to be suitable for breast conserving therapy including whole breast RT.
• Ability to tolerate protocol treatment.
• Protocol RT should preferably commence within 8 weeks but must commence no later than 12 weeks from the last surgical procedure.
• ECOG performance status 0, 1 or 2.
• Patient's life expectancy > 5 years.
• Availability for long-term follow-up.
• Written informed consent. Exclusion Criteria:

Patients who fulfill any of the following criteria are not eligible for admission to study:

• Multicentric disease or extensive microcalcifications that could not be completely excised by breast conserving surgery with radial margins of =1 mm*. *Patients with superficial and/or deep margin of <1 mm are eligible if surgery has removed all of the intervening breast tissue from the subcutaneous tissue to the pectoralis fascia.
• Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical examination (if lymph node biopsy or dissection has been performed).
• Locally recurrent breast cancer.
• Previous DCIS or invasive cancer of the contralateral breast.
• Bilateral DCIS of the breasts
• Synchronous invasive carcinoma of the contralateral breast
• Other concurrent or previous malignancies except:
• Non-melanomatous skin cancer;
• Carcinoma in situ of the cervix or endometrium; and
• Invasive carcinoma of the cervix, endometrium, colon, thyroid and melanoma treated at least five years prior to study admission without disease recurrence.
• Serious non-malignant disease that precludes definitive surgical or radiation treatment (e.g., scleroderma, systemic lupus erythematosus, cardiovascular/pulmonary/renal disease).
• ECOG performance status = 3.
• Women who are pregnant or lactating.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating

Intervention

Radiation:
• Standard WB fractionation
A total dose of 50 Gy in 25 fractions in 2-Gy daily fractions, 5 fractions per week (at least 9 fractions per fortnight).
• Shorter WB fractionation
A total dose of 42.5 Gy in 16 fractions in 2.656-Gy daily fractions, 5 fractions per week (at least 9 fractions per fortnight).
• Standard WB fractionation+Boost
Whole Breast: A total dose of 50 Gy in 25 fractions in 2-Gy daily fractions, 5 fractions per week (at least 9 fractions per fortnight). Tumour bed: A total dose of 10 Gy in 5 fractions in 2-Gy daily fractions, 5 fractions per week.
• Shorter WB fractionation + Boost
Whole breast: A total dose of 42.5 Gy in 16 fractions in 2.656-Gy daily fractions, 5 fractions per week (at least 9 fractions per fortnight). Tumour bed: A total dose of 10 Gy in 4 fractions in 2.5-Gy daily fractions, 4 fractions per week.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Premion - Wesley	Auchenflower	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	Barwon Health - Andrew Love Cancer Care Centre, Geelong Hospital	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Cancer Care Centre	Kingswood	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Austin Hospital	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	William Buckland Radiotherapy Centre, Alfred Hospital	Melbourne	Victoria
Australia	Genesis Cancer Care (previously Premion) - Nambour	Nambour	Queensland
Australia	Sir Charles Gardiner Hospital	Nedlands	Western Australia
Australia	Perth Radiation Oncology	Perth	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Radiation Oncology - Mater Centre	South Brisbane	Queensland
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Toowoomba Cancer Research Centre	Toowoomba	Queensland
Australia	North Queensland Oncology Service	Townsville	Queensland
Australia	Genesis Cancer Care (previously Premion) - Tugun	Tugun	Queensland
Australia	Riverina Cancer Care Centre	Wagga Wagga	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Wentworthville	New South Wales
Belgium	Onze Lieve Vrouw Ziekenhuis	Aalst
Belgium	ZNA Middelheim	Antwerpen
Belgium	Cliniques Univeritaires St Luc	Brussel
Belgium	Universitair Zielenhusi	Brussel
Belgium	Hopital De Jolimont	Haine St Paul
Belgium	AZ Groeninghe - Campus Maria's Voorzienigheid	Kortrijk
Belgium	Algemeen Ziekenhis Sint-Augustinus	Wilrijk
Canada	Nova Scotia Cancer Centre	Halifax
Canada	Jurvanski Cancer Centre	Hamilton
Canada	Notre Dame Hospital	Hearst
Canada	BCCA Southern Interior - CAVK	Kelowna
Canada	London Regional Cancer Program	London
Canada	Saint John Regional Hospital	Miramichi
Canada	Leon Richard Oncology Centre	Moncton
Canada	Hospital Maisonneuve-Rosemont	Montreal
Canada	Lakeridge Health	Oshawa
Canada	CHUQ L'Hotel-Dieu de Quebec	Quebec
Canada	McGill University Department of Oncology	Sainte-Anne-de-Bellevue
Canada	Allan Blair Cancer Centre	Saskatoon
Canada	Saskatoon Cancer Centre	Saskatoon
Canada	Universite de Sherbrooke - CUGH	Sherbrooke
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay
Canada	Odette Cancer Centre	Toronto
Canada	Princess Margaret Hospital	Toronto
Canada	BCCA Vancouver Centre	Victoria
Canada	Vancouver Island Cancer Centre	Victoria
Canada	Cancer Care Manitoba	Winnipeg
France	Chr De Grenoble - La Tronche	Grenoble
France	Centre Antine Lacassagne	Nice
Ireland	Cork University Hospital	Cork
Ireland	University Hospital Galway	Galway
Ireland	SLRON (St Luke's Rad Onc Network)	Rathgar
Italy	Centro Di Riferimento Oncologico - Aviano	Aviano
Italy	Fondazione Salvatore Maugeri	Pavia
Netherlands	Cancer Institute Antoni Van Leeuwenhoekziekenhuis	Amsterdam
Netherlands	Academisch Medisch Centrum	Amsterdam,
Netherlands	Arnhem 'S Radiotherapeutisch Instituut	Arnhem
Netherlands	Reinier de Graaf Groep	Delft
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Leiden University Medical Centre	Leiden
Netherlands	Maastricht Radiation Oncology Maastro Clinic	Maastricht
Netherlands	Medisch Centrum Haaglanden	Westeinde
Netherlands	ISALA Klinieken	Zwolle
New Zealand	Auckland Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
Singapore	National University Hospital	Singapore
Switzerland	University Hospital Basel	Basel
Switzerland	IOSI	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubunden	Chur
Switzerland	Kantonsspital Munsterlingen	Munsterlingen
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Brust-Zentrum Zurich-Seefeld	Zurich
Switzerland	Klinik Hirslanden	Zurich
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Basildon University Hospital	Basildon
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Sandwell and West Birmingham Hospitals NHS Trust	Birmingham
United Kingdom	Pilgram Hospital	Boston	Lincolnshire
United Kingdom	Bristol Haematology & Oncology	Bristol
United Kingdom	Queens Hospital Burton	Burton-On-Trent	Staffordshire
United Kingdom	Gloucestershire Royal & Cheltenham General Hospitals	Cheltenham	Gloucestershire
United Kingdom	Colchester Hospital	Colchester
United Kingdom	Coventry Arden Cancer Centre	Coventry
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Dumfries & Galloway Royal Infirmary	Dumfries
United Kingdom	Queen Margaret Hospital	Dunfermline
United Kingdom	Edinburgh Western General Hospital	Edinburgh
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	Ipswich Hospital	Ipswich
United Kingdom	Kidderminster Hospital	Kidderminster
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Imperial College Healthcare Charing Cross	London
United Kingdom	James Cook University Hospital	Middlesborough
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex
United Kingdom	Nottingham University Hospitals	Nottingham
United Kingdom	Churchill Hospital	Oxford	Headington
United Kingdom	Royal Alexandra Hospital	Paisley
United Kingdom	Alexandra Hospital	Redditch
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	The Shrewsbury and Telford Hospital NHS Trust	Shrewsbury
United Kingdom	Ealing Hospital	Southall	Middlesex
United Kingdom	Southend University Hopstial	Southend
United Kingdom	Stafford Hospital	Stafford
United Kingdom	University of North Staffordshire	Stoke-On-Trent	Staffordshire
United Kingdom	Royal Marsden	Sutton
United Kingdom	Kings Mill Hospital Nottingham	Sutton-In-Ashfield	Nottinghamshire
United Kingdom	Musgrove Park Hospital	Taunton	Somerset
United Kingdom	Warwick Hospital	Warwick
United Kingdom	New Cross Hospital	Wolverhampton

Sponsors (8)

Lead Sponsor	Collaborator
Trans Tasman Radiation Oncology Group	Borstkanker Onderzoek Groep, Breast International Group, Cancer Trials Ireland, ETOP IBCSG Partners Foundation, European Organisation for Research and Treatment of Cancer - EORTC, NCIC Clinical Trials Group, Scottish Cancer Trials Breast Group

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  France,  Ireland,  Italy,  Netherlands,  New Zealand,  Singapore,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to local recurrence, measured from the date of randomization to the date of first evidence of local recurrence.		Main analysis after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Secondary	Overall survival		Measured from the date of randomization to the date of death from any cause. Main analysis of secondary outcomes after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Secondary	Time to disease recurrence		Measured from the date of randomization to the date of first evidence of recurrent disease. Main analysis of secondary outcomes after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Secondary	Cosmetic Outcome		Cosmetic assessment will take place at baseline, 12, 36 and 60 months post RT.
Secondary	Radiation toxicity		Assessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10.
Secondary	Quality of Life change		Assessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT.

External Links

•   Click here for more information about this study on the TROG official website