Intensity Modulated Radiotherapy (IMRT) vs. 3D-conformal Accelerated Partial Breast Irradiation (APBI) for Early Stage Breast Cancer After Lumpectomy (2009-APBI)

A Phase III Randomized Study Comparing Intensity Modulated Planning Versus 3-Dimensional Planning for Accelerated Partial Breast Radiotherapy

In the setting of radiotherapy as part of breast-conservation therapy for patients with early stage breast cancer, the novel planning and delivery method of intensity modulated radiotherapy is an effective and safe alternative to the commonly-used standard 3D-conformal external beam radiotherapy, spares more normal breast and lung tissue, and may lead to improved clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: accelerated partial breast irradiation - IMRT planning; Radiation: accelerated partial breast irradiation - 3D-conformal planning

• Study Type: Interventional
• Enrollment (Anticipated): 660
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rachel Lei, BS; Phone Number: 303-418-7607; Email: rachel.lei@usoncology.com
• Study Contact Backup: Name: Charles Leonard, MD; Phone Number: 303-730-4700

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Recruiting
      • Rocky Mountain Cancer Centers - Aurora
      • Sub-Investigator: William Daniel, MD
      • Sub-Investigator: Kathryn Howell, MD
      • Sub-Investigator: Dennis Carter, MD
    • Boulder, Colorado, United States, 80303
      • Recruiting
      • Rocky Mountain Cancer Centers - Boulder
      • Sub-Investigator: Andrew Antell, MD
      • Sub-Investigator: Meera Patel, MD
      • Sub-Investigator: Ralph Wright, MD
    • Lakewood, Colorado, United States, 80228
      • Recruiting
      • Rocky Mountain Cancer Centers - Lakewood
      • Sub-Investigator: Ralph Wright, MD
      • Principal Investigator: Charles Leonard, MD
    • Littleton, Colorado, United States, 80120
      • Recruiting
      • Rocky Mountain Cancer Centers - Littleton
      • Sub-Investigator: Kathryn Howell, MD
      • Principal Investigator: Charles Leonard, MD
    • Thornton, Colorado, United States, 80260
      • Recruiting
      • Rocky Mountain Cancer Centers - Thornton
      • Sub-Investigator: Robert LaPorte, MD
      • Sub-Investigator: Daniel Chin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed disease (AJC Classification): Tis, T1, T2 (≤ 3.0 cm), N0, M0.
• Microscopic multifocal disease is only allowed when the entire span of identified disease measures 3.0 cm or less.
• Negative surgical margins ( ≥ 0.2 cm) after final surgery.
• Subjects with infiltrating lobular histologies or high nuclear grade DCIS will be required to have breast MRI scanning as part of the initial staging to verify localized disease.
• Subjects with DCIS will be included in the study only if they had an MRI prior to lumpectomy.
• Findings on MRI scanning revealing relevant suspicion of disease outside of planned lumpectomy volume should be further evaluated by ultrasound and, if necessary biopsy, to exclude multicentric/multifocal disease.
• Subjects with malignant calcifications on mammography will be required to have repeat mammography after surgery to ensure removal of all malignant calcifications.
• Willing to complete additional screening requirements and meet eligibility criteria as defined in protocol Sec. 4.4.
• Successful placement of fiducial markers for IGRT requiring nonmigrating fiducials.
• PTV to ipsilateral breast ratio (IBR) ≤ 25 %.
• Radiotherapy anticipated to begin within 10 weeks of lumpectomy or re-excision of margins.

Exclusion Criteria:

• Pregnancy or breast-feeding.
• Have collagen-vascular disease.
• Inadequate surgical margins ( < 0.2 cm) after final surgery.
• Subjects with persistent malignant/suspicious micro-calcifications.
• Gross multifocal disease and microscopic disease greater than 3.0 cm.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMRT; Intensity modulated radiotherapy, 38.5 Gy, 10 fractions over 5 days	Radiation: accelerated partial breast irradiation - IMRT planning; 38.5 Gy, 10 fractions over 5 days; Other Names: EBRT; APBI
Active Comparator: 3D-CRT; Three dimensional conformal external radiotherapy, 38.5 Gy, 10 fractions over 5 days	Radiation: accelerated partial breast irradiation - 3D-conformal planning; 38.5 Gy, 10 fractions over 5 days; Other Names: EBRT; APBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of breast pain after Accelerated Partial Breast Radiotherapy (APBI)	Assessment by both treating investigators and by subjective patient outcomes questionnaires filled out at each follow-up visit	5 years
Prevalence of chest wall pain after Accelerated Partial Breast Radiotherapy (APBI)	Assessment by both treating investigators and by subjective patient outcomes questionnaires filled out at each follow-up visit	2-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetric comparison	Comparison of treatment plans and actual doses received between comparable patients treated with 3D-CRT and IMRT with regard to treatment target and normal tissue	5-10 days
Acute skin reactions	Radiation-induced dermatitis	6 months
Cosmetic outcomes after APBI	Assesed by both treating investigators and subjective patient questionnaires filled out at each follow-up visit	2-5 years
Ipsilateral breast event	Track occurrence and patterns of local treatment failures or new primaries within the treated breast (efficacy outcome measure)	5-15 years
Cause specific survival	Track survival status and the specific cause(s) of death if applicable for study participants (efficacy outcome measure)	5-15 years
Disease free survival	Track breast-cancer free survival status of study participants (efficacy outcome measure)	5-15 years
Overall survival	Track the overall survival status of all study participants (efficacy outcome measure)	5-15 years

Collaborators and Investigators

• Sponsor: Rocky Mountain Cancer Centers
• Investigators: Principal Investigator: Charles Leonard, MD, Rocky Mountain Cancer Centers

Publications and helpful links

General Publications

• Leonard CE, Wang Y, Asmar L, Lei RY, Howell KT, Henkenberns PL, Johnson TK, Hobart TL, Tole SP, Kercher JM, Widner JL, Barke L, Kaske T, Carter DL. A prospective Phase III trial evaluating patient self-reported pain and cosmesis in accelerated partial breast irradiation utilizing 3-D versus intensity-modulated radiotherapy. Cancer Med. 2021 Oct;10(20):7089-7100. doi: 10.1002/cam4.4242. Epub 2021 Sep 1.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2028

Study Registration Dates

• First Submitted: August 18, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: breast cancer; IMRT; DCIS; intensity modulated radiotherapy; accelerated partial breast irradiation; lumpectomy; APBI; adjuvant radiotherapy; 3D CRT; early-stage breast cancer; breast-conservation; three dimensional conformal external radiotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2009-APBI; WIRB #20091193 (Other Identifier: Western IRB)