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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Trans-Tasman Radiation Oncology Group (TROG)
Sponsor:
Collaborators:
Breast International Group
NCIC Clinical Trials Group
ICORG- All Ireland Cooperative Oncology Research Group
Borstkanker Onderzoek Groep
International Breast Cancer Study Group
Scottish Cancer Trials Breast Group (SCTBG)
European Organisation for Research and Treatment of Cancer - EORTC
Australian New Zealand Breast Cancer Trials Group
Information provided by (Responsible Party):
Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier:
NCT00470236
First received: May 3, 2007
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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.

Condition Intervention Phase
Carcinoma, Ductal, Breast
Radiation: Standard WB fractionation
Radiation: Shorter WB fractionation
Radiation: Standard WB fractionation+Boost
Radiation: Shorter WB fractionation + Boost
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Trans-Tasman Radiation Oncology Group (TROG):

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Cosmetic Outcome [ Time Frame: Cosmetic assessment will take place at baseline, 12, 36 and 60 months post RT. ] [ Designated as safety issue: No ]
  • Radiation toxicity [ Time Frame: Assessed at baseline, last week of RT, 3, 6, and 12 months post RT and then yearly until year 10. ] [ Designated as safety issue: Yes ]
  • Quality of Life [ Time Frame: Assessed at baseline, last week of RT, 6, 12, 24, 60 & 120 months post RT. ] [ Designated as safety issue: No ]

Estimated Enrollment: 1600
Study Start Date: June 2007
Estimated Study Completion Date: November 2025
Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 (Standard WB Fractionation)
Whole Breast RT alone - Standard fractionation schedule (50GY/25 Fractions/35days)
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).
Other Name: Radiation
Experimental: Arm 2 (Shorter WB Fractionation)
Whole Breast RT alone - Shorter fractionation schedule (42.5 Gy/16 fractions/22 days)
Radiation: 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).
Other Name: Radiation
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)
Radiation: 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.

Other Name: Radiation
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)
Radiation: 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.

Other Name: Radiation

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470236

Contacts
Contact: Boon Chua +61 3 9656 1111 ext 1145 Boon.Chua@petermac.org

  Show 110 Study Locations
Sponsors and Collaborators
Trans-Tasman Radiation Oncology Group (TROG)
Breast International Group
NCIC Clinical Trials Group
ICORG- All Ireland Cooperative Oncology Research Group
Borstkanker Onderzoek Groep
International Breast Cancer Study Group
Scottish Cancer Trials Breast Group (SCTBG)
European Organisation for Research and Treatment of Cancer - EORTC
Australian New Zealand Breast Cancer Trials Group
Investigators
Study Chair: Boon Chua Peter MacCallum Cancer Centre, Australia
  More Information

Additional Information:
No publications provided

Responsible Party: Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier: NCT00470236     History of Changes
Other Study ID Numbers: TROG 07.01, NHMRC 454390, BIG 3-07, NCIC CTG MA.33, BOOG 2009-03, ICORG 10-06, EORTC 22085-10083, IBCSG 38-10, SCTBG 2009MayPR55
Study First Received: May 3, 2007
Last Updated: June 5, 2013
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by Trans-Tasman Radiation Oncology Group (TROG):
Ductal carcinoma in-situ
Breast conserving therapy
Whole breast radiation therapy
Tumour bed boost
Fractionation schedules
Completely excised non-low risk DCIS

Additional relevant MeSH terms:
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 22, 2014