Overview

This trial is active, not recruiting.

Condition carcinoma, ductal, breast
Treatments standard wb fractionation, shorter wb fractionation, standard wb fractionation+boost, shorter wb fractionation + boost
Phase phase 3
Sponsor Trans-Tasman Radiation Oncology Group (TROG)
Collaborator Breast International Group
Start date June 2007
End date June 2024
Trial size 1608 participants
Trial identifier NCT00470236, BIG 3-07, BOOG 2009-03, EORTC 22085-10083, IBCSG 38-10, ICORG 10-06, NCIC CTG MA.33, NHMRC 454390, SCTBG 2009MayPR55, TROG 07.01

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Whole Breast RT alone - Standard fractionation schedule (50GY/25 Fractions/35days)
standard wb fractionation Radiation
A total dose of 50 Gy in 25 fractions in 2-Gy daily fractions, 5 fractions per week (at least 9 fractions per fortnight).
(Experimental)
Whole Breast RT alone - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days)
shorter wb fractionation Radiation
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).
(Active Comparator)
Whole Breast RT + tumor bed boost - Standard fractionation schedule (50 Gy/25 fractions/35 days; Boost 16 Gy/8 fractions/10 days)
standard wb fractionation+boost Radiation
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.
(Experimental)
Whole breast RT + tumour bed boost - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days; Boost 16 Gy/8 fractions/10 days)
shorter wb fractionation + boost Radiation
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.

Primary Outcomes

Measure
Time to local recurrence, measured from the date of randomization to the date of first evidence of local recurrence.
time frame: Main analysis after all patients have completed 5 years of follow-up. Updated analysis after 10 years of follow-up.

Secondary Outcomes

Measure
Overall survival
time frame: 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.
Time to disease recurrence
time frame: 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.
Cosmetic Outcome
time frame: Cosmetic assessment will take place at baseline, 12, 36 and 60 months post RT.
Radiation toxicity
time frame: Assessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10.
Quality of Life
time frame: Assessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT.

Eligibility Criteria

Female participants at least 18 years old.

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.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Trans-Tasman Radiation Oncology Group (TROG).