Clinical Trials /

APBI: 27Gy in 5 Fractions for Early Breast Cancer

NCT02681107

Description:

This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which is expected to be equally tolerated as standard whole breast irradiation (WBI) based on radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and less costly than 3-6 weeks of standard WBI. 274 women will be treated. Rates of fibrosis and cosmesis at 2 years will be compared to data already collected using standard WBI in the Canadian RAPID trial.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: APBI: 27Gy in 5 Fractions for Early Breast Cancer
  • Official Title: Accelerated Partial Breast Irradiation Using Five Daily Fractions: A Single Arm, Phase II, Prospective Cohort Study to Examine Cosmetic Outcomes and Toxicity (The ACCEL Trial)

Clinical Trial IDs

  • ORG STUDY ID: HREBA.CC-16-0006
  • SECONDARY ID: No. 11629-27/5-01
  • NCT ID: NCT02681107

Conditions

  • Breast Cancer

Purpose

This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which is expected to be equally tolerated as standard whole breast irradiation (WBI) based on radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and less costly than 3-6 weeks of standard WBI. 274 women will be treated. Rates of fibrosis and cosmesis at 2 years will be compared to data already collected using standard WBI in the Canadian RAPID trial.

Detailed Description

      Background: Previously, accelerated partial breast irradiation (APBI) using 3D conformal
      external beam techniques to deliver 38.5Gy in 10, twice daily, fractions caused worse
      fibrosis and cosmetic deterioration than standard whole breast irradiation (WBI) following
      breast conserving surgery (BCS) for women with early breast cancer. Over the decade since the
      original APBI technique was designed, long-term outcomes of various breast RT fractionation
      regimens have become available and suggest that normal tissue fibrosis and cosmesis varies
      with the radiobiological constant: α/β=2 rather than α/β=3.4 as previously estimated.
      Radiobiologic modeling using α/β=2, indicates that a dose of 27Gy in 5 daily treatments
      should result in comparable late effects as 42.5Gy in 16, or 50Gy in 25 fractions. This
      clinical trial will validate the safety of a short, convenient and less costly APBI using
      27Gy in 5 daily fractions.

      Objective: To determine the cosmetic and normal tissue outcomes of APBI using 3D-conformal RT
      with 27Gy in 5 fractions over 1 week.

      Methods: A single-arm, phase II, non-inferiority, prospective study will be conducted. 274
      women with newly diagnosed, invasive or in-situ ductal carcinoma treated with BCS and
      sentinel lymph node biopsy (or axillary dissection) who are candidates for WBI alone, will be
      treated. Subjects will be age 50 years and older, with tumors less than 3cm diameter, with
      negative margins and nodes and with excellent or good baseline cosmetic outcome following
      BCS. Patients with extensive ductal carcinoma in-situ, BRCA mutations, Grade 3 cancers with
      lymphatic or vascular invasion, or lobular carcinoma will be excluded. These selection
      criteria are similar to the Canadian RAPID trial. In the first phase of the study, 150
      patients will be recruited and interim analyses will be conducted to rule out unacceptable
      toxicity at 2 years.

      Study endpoints: The primary endpoint will be the proportion of women who retain an Excellent
      or Good cosmetic score at 2 years using the EORTC Cosmetic Rating System and clinical
      photographs taken prior to, and at 1 and 2 years after RT. Secondary endpoints will include
      rates and grades of breast fibrosis, induration, telangiectasia, breast pain, ipsilateral
      breast tumor recurrence, overall and breast cancer-specific survival and subsequent
      mastectomy rates.

      Sample size, statistical analyses: In the RAPID trial, 88% of patients with Excellent or Good
      cosmesis prior to RT had Excellent or Good scores at 3 years. Only patients with
      Excellent/Good cosmesis at baseline will be included in the current study. The proportion of
      women with Excellent/Good cosmesis at 1 and 2 years will be calculated. Using 80% power, a
      non-inferiority margin of 0.08 and a one-sided binomial test for non-inferiority and a
      significance level of 0.05, will require a sample size of 249 women with evaluable 2-yr
      cosmesis. 274 patients will be recruited to allow for a 10% drop-out rate. To ensure safety,
      a first interim analysis with Grade 2 or higher breast fibrosis as the primary endpoint, will
      be conducted when 50 patients have completed their 1-year assessment and repeated when 50
      patients have completed their 2-year follow up. If the rate of Grade 2 or higher fibrosis
      exceeds 5% at either time point, trial accrual will be suspended.

      Feasibility: Over 600 women eligible for this protocol receive RT in Alberta each year. If
      30% accept study participation, accrual will be complete in <2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalSingle cohort to receive Accelerated Partial Breast Irradiation (APBI) 27Gy in 5 fractions

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Female, with new invasive or in-situ ductal carcinoma of the breast
    
              -  Treated with Breast conserving surgery (BCS) with negative margins
    
              -  pN0 on sentinel node biopsy or axillary dissection; cN0 if DCIS alone
    
              -  Maximum pathologic tumor diameter is 3.0 cm (invasive or DCIS)
    
              -  No clinical or imaging evidence of distant metastases
    
              -  Age 50 years or older at diagnosis
    
              -  No contraindications to breast irradiation
    
              -  Excellent or Good overall cosmetic score at baseline following BCS
    
              -  Able and willing to provide written informed consent
    
              -  Available for 2 year follow up at the treating RT centre
    
            Exclusion Criteria:
    
              -  Age < 50 years at diagnosis
    
              -  BRCA 1 or 2 pathogenic mutation
    
              -  Pathologic tumor diameter >3cm (including DCIS+invasive disease)
    
              -  Lobular histology alone
    
              -  Triple negative (ER-, PR-, HER2-) or HER2 overexpressing disease
    
              -  Margin (other than deep) <2 mm
    
              -  Presence of both Grade 3 and lymphatic or vascular invasion
    
              -  Fair or Poor overall cosmetic score at baseline following BCS
    
              -  Presence of ipsilateral breast implants
    
              -  Inability to develop an APBI plan meeting all dosimetry constraints
    
              -  Unable to start RT within 16 weeks of BCS or 8 weeks of last iv chemotherapy
    
              -  Unable or unwilling to sign informed consent document or attend for 2-year cosmetic
                 assessment at the treating RT centre
    
              -  Potential contraindications for breast RT including a confirmed diagnosis of lupus,
                 scleroderma, or pregnancy
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:50 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Rate of Excellent or Good Global cosmetic score
    Time Frame:2 years
    Safety Issue:
    Description:Global cosmetic score assessed by trained observers and patients themselves using the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer rating system for cosmetic assessment; rate of deterioration from Excellent/Good to Fair Poor. This will be augmented by assessment of clinical photographs prior to and at 1 and 2 years after radiation therapy (RT).

    Secondary Outcome Measures

    Measure:Breast induration
    Time Frame:2 years
    Safety Issue:
    Description:Radiation Therapy Oncology Group (RTOG) Late Radiation Morbidity Scoring Scheme, rate of Grade 2+ subcutaneous fibrosis
    Measure:Breast pain
    Time Frame:2 years
    Safety Issue:
    Description:Patient reported average and worst pain in the treated breast over the week prior to assessment
    Measure:Local recurrence
    Time Frame:2 and 5 years
    Safety Issue:
    Description:Any new invasive or in situ breast cancer within the ipsilateral breast

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:AHS Cancer Control Alberta

    Trial Keywords

    • Radiation therapy
    • Accelerated partial breast irradiation (APBI)
    • Breast conserving surgery
    • Stage 1

    Last Updated