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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00470236




Registration number
NCT00470236
Ethics application status
Date submitted
3/05/2007
Date registered
7/05/2007
Date last updated
22/03/2023

Titles & IDs
Public title
Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast
Scientific title
A Randomised Phase III Study of Radiation Doses and Fractionation Schedules in Non-low Risk Ductal Carcinoma In Situ (DCIS) of the Breast
Secondary ID [1] 0 0
NHMRC 454390
Secondary ID [2] 0 0
TROG 07.01
Universal Trial Number (UTN)
Trial acronym
DCIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Ductal, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Cervical (cervix)
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Standard WB fractionation
Treatment: Other - Shorter WB fractionation
Treatment: Other - Standard WB fractionation+Boost
Treatment: Other - Shorter WB fractionation + Boost

Active comparator: Arm 1 (Standard WB Fractionation) - Whole Breast RT alone - Standard fractionation schedule (50GY/25 Fractions/35days)

Experimental: Arm 2 (Shorter WB Fractionation) - Whole Breast RT alone - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days)

Active comparator: Arm 3 (Standard WB fractionation+Boost) - Whole Breast RT + tumor bed boost - Standard fractionation schedule (50 Gy/25 fractions/35 days; Boost 16 Gy/8 fractions/10 days)

Experimental: Arm 4 (Shorter WB fractionation + Boost) - Whole breast RT + tumour bed boost - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days; Boost 16 Gy/8 fractions/10 days)


Treatment: Other: 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).

Treatment: Other: 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).

Treatment: Other: 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.

Treatment: Other: 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.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to local recurrence, measured from the date of randomization to the date of first evidence of local recurrence.
Timepoint [1] 0 0
Main analysis after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
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 outcome [2] 0 0
Time to disease recurrence
Timepoint [2] 0 0
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 outcome [3] 0 0
Cosmetic Outcome
Timepoint [3] 0 0
Cosmetic assessment will take place at baseline, 12, 36 and 60 months post RT.
Secondary outcome [4] 0 0
Radiation toxicity
Timepoint [4] 0 0
Assessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10.
Secondary outcome [5] 0 0
Quality of Life change
Timepoint [5] 0 0
Assessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2024
Actual
Sample size
Target
Accrual to date
Final
1608
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 0 0
Nepean Cancer Care Centre - Kingswood
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 0 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [7] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [8] 0 0
Westmead Hospital - Wentworthville
Recruitment hospital [9] 0 0
Premion - Wesley - Auchenflower
Recruitment hospital [10] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [11] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [12] 0 0
Genesis Cancer Care (previously Premion) - Nambour - Nambour
Recruitment hospital [13] 0 0
Radiation Oncology - Mater Centre - South Brisbane
Recruitment hospital [14] 0 0
Toowoomba Cancer Research Centre - Toowoomba
Recruitment hospital [15] 0 0
North Queensland Oncology Service - Townsville
Recruitment hospital [16] 0 0
Genesis Cancer Care (previously Premion) - Tugun - Tugun
Recruitment hospital [17] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [18] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [19] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [20] 0 0
Barwon Health - Andrew Love Cancer Care Centre, Geelong Hospital - Geelong
Recruitment hospital [21] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [22] 0 0
Austin Hospital - Melbourne
Recruitment hospital [23] 0 0
William Buckland Radiotherapy Centre, Alfred Hospital - Melbourne
Recruitment hospital [24] 0 0
Sir Charles Gardiner Hospital - Nedlands
Recruitment hospital [25] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [26] 0 0
Perth Radiation Oncology - Perth
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
- Kingswood
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2065 - St Leonards
Recruitment postcode(s) [6] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [7] 0 0
2298 - Waratah
Recruitment postcode(s) [8] 0 0
2145 - Wentworthville
Recruitment postcode(s) [9] 0 0
4006 - Auchenflower
Recruitment postcode(s) [10] 0 0
4006 - Brisbane
Recruitment postcode(s) [11] 0 0
4102 - Brisbane
Recruitment postcode(s) [12] 0 0
- Nambour
Recruitment postcode(s) [13] 0 0
4101 - South Brisbane
Recruitment postcode(s) [14] 0 0
- Toowoomba
Recruitment postcode(s) [15] 0 0
4810 - Townsville
Recruitment postcode(s) [16] 0 0
4224 - Tugun
Recruitment postcode(s) [17] 0 0
5000 - Adelaide
Recruitment postcode(s) [18] 0 0
7000 - Hobart
Recruitment postcode(s) [19] 0 0
7250 - Launceston
Recruitment postcode(s) [20] 0 0
3220 - Geelong
Recruitment postcode(s) [21] 0 0
3002 - Melbourne
Recruitment postcode(s) [22] 0 0
3084 - Melbourne
Recruitment postcode(s) [23] 0 0
3181 - Melbourne
Recruitment postcode(s) [24] 0 0
6009 - Nedlands
Recruitment postcode(s) [25] 0 0
6001 - Perth
Recruitment postcode(s) [26] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Aalst
Country [2] 0 0
Belgium
State/province [2] 0 0
Antwerpen
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussel
Country [4] 0 0
Belgium
State/province [4] 0 0
Haine St Paul
Country [5] 0 0
Belgium
State/province [5] 0 0
Kortrijk
Country [6] 0 0
Belgium
State/province [6] 0 0
Wilrijk
Country [7] 0 0
Canada
State/province [7] 0 0
Halifax
Country [8] 0 0
Canada
State/province [8] 0 0
Hamilton
Country [9] 0 0
Canada
State/province [9] 0 0
Hearst
Country [10] 0 0
Canada
State/province [10] 0 0
Kelowna
Country [11] 0 0
Canada
State/province [11] 0 0
London
Country [12] 0 0
Canada
State/province [12] 0 0
Miramichi
Country [13] 0 0
Canada
State/province [13] 0 0
Moncton
Country [14] 0 0
Canada
State/province [14] 0 0
Montreal
Country [15] 0 0
Canada
State/province [15] 0 0
Oshawa
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Canada
State/province [17] 0 0
Sainte-Anne-de-Bellevue
Country [18] 0 0
Canada
State/province [18] 0 0
Saskatoon
Country [19] 0 0
Canada
State/province [19] 0 0
Sherbrooke
Country [20] 0 0
Canada
State/province [20] 0 0
Thunder Bay
Country [21] 0 0
Canada
State/province [21] 0 0
Toronto
Country [22] 0 0
Canada
State/province [22] 0 0
Victoria
Country [23] 0 0
Canada
State/province [23] 0 0
Winnipeg
Country [24] 0 0
France
State/province [24] 0 0
Grenoble
Country [25] 0 0
France
State/province [25] 0 0
Nice
Country [26] 0 0
Ireland
State/province [26] 0 0
Cork
Country [27] 0 0
Ireland
State/province [27] 0 0
Galway
Country [28] 0 0
Ireland
State/province [28] 0 0
Rathgar
Country [29] 0 0
Italy
State/province [29] 0 0
Aviano
Country [30] 0 0
Italy
State/province [30] 0 0
Pavia
Country [31] 0 0
Netherlands
State/province [31] 0 0
Amsterdam,
Country [32] 0 0
Netherlands
State/province [32] 0 0
Amsterdam
Country [33] 0 0
Netherlands
State/province [33] 0 0
Arnhem
Country [34] 0 0
Netherlands
State/province [34] 0 0
Delft
Country [35] 0 0
Netherlands
State/province [35] 0 0
Groningen
Country [36] 0 0
Netherlands
State/province [36] 0 0
Leiden
Country [37] 0 0
Netherlands
State/province [37] 0 0
Maastricht
Country [38] 0 0
Netherlands
State/province [38] 0 0
Westeinde
Country [39] 0 0
Netherlands
State/province [39] 0 0
Zwolle
Country [40] 0 0
New Zealand
State/province [40] 0 0
Auckland
Country [41] 0 0
New Zealand
State/province [41] 0 0
Christchurch
Country [42] 0 0
New Zealand
State/province [42] 0 0
Hamilton
Country [43] 0 0
Singapore
State/province [43] 0 0
Singapore
Country [44] 0 0
Switzerland
State/province [44] 0 0
Basel
Country [45] 0 0
Switzerland
State/province [45] 0 0
Bellinzona
Country [46] 0 0
Switzerland
State/province [46] 0 0
Bern
Country [47] 0 0
Switzerland
State/province [47] 0 0
Chur
Country [48] 0 0
Switzerland
State/province [48] 0 0
Munsterlingen
Country [49] 0 0
Switzerland
State/province [49] 0 0
St. Gallen
Country [50] 0 0
Switzerland
State/province [50] 0 0
Zurich
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Gloucestershire
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Headington
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Lincolnshire
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Middlesex
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Nottinghamshire
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Somerset
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Staffordshire
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Aberdeen
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Basildon
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Belfast
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Birmingham
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Bristol
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Colchester
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Coventry
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Derby
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Dumfries
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Dunfermline
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Edinburgh
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Glasgow
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Guildford
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Ipswich
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Kidderminster
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Leicester
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Lincoln
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Middlesborough
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Nottingham
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Paisley
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Redditch
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Sheffield
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Shrewsbury
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Southend
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Stafford
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Sutton
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Warwick
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Other
Name
Trans Tasman Radiation Oncology Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Breast International Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
NCIC Clinical Trials Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer Trials Ireland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Borstkanker Onderzoek Groep
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
ETOP IBCSG Partners Foundation
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Scottish Cancer Trials Breast Group
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT00470236
Trial related presentations / publications
Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G, Bryant G, Ahern V, Purohit K, Graham PH, Akra M, McArdle O, O'Brien P, Harvey JA, Kirkove C, Maduro JH, Campbell ID, Delaney GP, Martin JD, Vu TTT, Muanza TM, Neal A, Olivotto IA; BIG 3-07/TROG 07.01 trial investigators. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022 Aug 6;400(10350):431-440. doi: 10.1016/S0140-6736(22)01246-6.
King MT, Link EK, Whelan TJ, Olivotto IA, Kunkler I, Westenberg AH, Gruber G, Schofield P, Chua BH; BIG 3-07/TROG 07.01 trial investigators. Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):685-698. doi: 10.1016/S1470-2045(20)30085-1. Epub 2020 Mar 20.
Public notes

Contacts
Principal investigator
Name 0 0
Boon Chua
Address 0 0
Prince of Wales Hospital Randwick
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00470236