Radiation Therapy in Treating Women With Early Stage Breast Cancer

Safety and Feasibility of Accelerated, Hypofractionated Radiotherapy in Women With Breast Cancer: A Phase II Trial

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in different ways may kill more tumor cells. Giving it after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects of radiation therapy and to see how well it works in treating women with early stage breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: External beam boost; Radiation: whole breast irradiation

Detailed Description

OBJECTIVES:

Primary

• To determine the freedom from local and regional failure in women with early stage breast cancer treated with accelerated, hypofractionated radiotherapy.
• To determine the acute and late toxicity of accelerated, hypofractionated radiotherapy using previously published toxicity scales.

Secondary

• To measure cosmesis using the Harvard cosmesis scale in patients who have undergone lumpectomy.
• To identify co-variates responsible for poor cosmetic outcome in these patients.

OUTLINE: Patients who have undergone lumpectomy undergo either intracavitary balloon brachytherapy boost and hypofractionated, accelerated whole breast irradiation (AWBI) OR 3D-conformal radiotherapy (3D-CRT)/intensity-modulated radiotherapy (IMRT) boost and AWBI. Patients who have undergone mastectomy undergo hypofractionated, accelerated chest wall irradiation.

• Intracavitary balloon brachytherapy boost and AWBI (post-lumpectomy): Patients undergo intracavitary balloon brachytherapy boost twice daily for 2 days (total of 4 fractions). Beginning 5-21 days after completion of brachytherapy, patients undergo AWBI once daily 5 days a week for approximately 2 weeks (total of 11 fractions).
• 3D-CRT/IMRT boost and AWBI (post-lumpectomy): Patients undergo 3D-CRT/IMRT boost twice daily for 2 days (total of 4 fractions). Patients also undergo AWBI as above before or after boost radiotherapy.
• Accelerated chest wall irradiation (post-mastectomy): Patients undergo accelerated chest wall irradiation once daily 5 days a week for approximately 2 weeks (total of 11 fractions).

Patients who have undergone lumpectomy undergo frontal digital photography of the breasts at baseline, immediately before the initiation of radiotherapy, and then annually for 3 years after completion of radiotherapy. These patients also complete the Breast Cancer Treatment Outcome Scale at baseline and at 3 years after completion of radiotherapy. Physicians complete the Harvard Cosmesis scale at baseline and at 1 and 3 years after completion of radiotherapy.

After completion of study treatment, patients are followed up at weeks 1, 4, and 8 and then every 4 months for 2 years, every 6 months for 3 years, and annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • RWJBarnabas Health - Robert Wood Johnson University Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08690
      • RWJBarnabas Health - Robert Wood Johnson University Hospital
    • Somerset, New Jersey, United States, 08873
      • RWJBarnabas Health - Robert Wood Johnson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer, including 1 of the following subtypes:

  • Ductal carcinoma in situ
  • Invasive ductal carcinoma
  • Invasive lobular carcinoma
  • Medullary carcinoma
  • Papillary carcinoma
  • Colloidal (mucinous) carcinoma
  • Tubular carcinoma

• Pathological stage 0-IIIA disease (pTis; pT1-2, N0-N2a, M0)

  • Tumor size ≤ 5 cm
• Breast considered technically satisfactory for radiotherapy

• Has undergone lumpectomy or mastectomy and either sentinel node biopsy or axillary dissection (if invasive carcinoma is present)

  • Negative inked histological margins (i.e., no invasive cells at surgical margin) or confirmed negative re-excision specimen
• Unifocal or multifocal (confined to 1 quadrant; tumors < 4 cm apart) disease with 1 or 2 foci that can be encompassed by 1 lumpectomy
• No proven multicentric carcinoma (tumors in different quadrants of the breast or tumor separated by ≥ 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy

• No evidence of suspicious microcalcifications in the breast before the start of radiotherapy

  • If malignancy-associated microcalcifications were initially present, the post-excision mammography must be negative
• No more than 9 positive axillary lymph nodes
• No palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor
• No previously treated contralateral breast cancer or synchronous ipsilateral breast cancer
• No lobular carcinoma in situ alone (i.e., no invasive component) or non-epithelial breast malignancies (e.g., sarcoma or lymphoma)
• No Paget disease of the nipple
• No skin involvement, regardless of tumor size
• No distant metastases
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Pre- or post-menopausal
• ECOG performance status 0-1
• No co-existing medical condition that would limit life expectancy to < 2 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except for nonmelanoma skin cancer (the disease-free interval from any prior malignancy must be continuous)
• No collagen vascular disease, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis
• No psychiatric or addictive disorder that would preclude obtaining informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior radiotherapy for the current breast cancer
• No tylectomies so extensive that the cosmetic result is low or poor prior to radiotherapy

• Chemotherapy allowed provided the following criteria are met:

  • Chemotherapy is not administered prior to, during, and for ≥ 21 days after completion of radiotherapy (for patients receiving brachytherapy boost)
  • Chemotherapy is not administered for ≥ 21 days before, during, and for ≥ 21 days after completion of radiotherapy (for patients receiving external beam radiotherapy boost or chest wall irradiation)

• Concurrent tamoxifen, anastrozole, or other hormonal therapy allowed

  • May be initiated before, during, or after radiotherapy
• No other concurrent chemotherapy, immunotherapy, or experimental medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; 3DCRT/IMRT lumpectomy bed boost followed by accelerated whole breast irradiation (AWBI)	Radiation: External beam boost; 3-dimensional conformal radiation therapy and intensity modulated radiation therapy; Radiation: whole breast irradiation; accelerated, hypofractionated whole breast irradiation
Active Comparator: B; Accelerated whole breast irradiation (AWBI) followed by 3DCRT/IMRT lumpectomy bed boost	Radiation: External beam boost; 3-dimensional conformal radiation therapy and intensity modulated radiation therapy; Radiation: whole breast irradiation; accelerated, hypofractionated whole breast irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Loco-regional control as assessed by physical examination, mammography, and other relevant imaging	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity (including seroma formation, brachial plexopathy, fat necrosis, pain, pigmentation, and telangiectasia) as assessed by NCI CTCAE v3.0	5 years
Cosmesis as assessed by the Breast Cancer Treatment Outcome Scale	5 years

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Bruce Haffty, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

General Publications

• Ahlawat S, Haffty BG, Goyal S, Kearney T, Kirstein L, Chen C, Moore DF, Khan AJ. Short-Course Hypofractionated Radiation Therapy With Boost in Women With Stages 0 to IIIa Breast Cancer: A Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2016 Jan 1;94(1):118-125. doi: 10.1016/j.ijrobp.2015.09.011. Epub 2015 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2009
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 28, 2009
• First Posted (Estimated): May 29, 2009

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage II breast cancer; stage I breast cancer; ductal breast carcinoma in situ; invasive ductal breast carcinoma; invasive lobular breast carcinoma; medullary ductal breast carcinoma with lymphocytic infiltrate; mucinous ductal breast carcinoma; papillary ductal breast carcinoma; tubular ductal breast carcinoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Pro20170001671; P30CA072720 (U.S. NIH Grant/Contract); CDR0000643276 (Other Identifier: NIH); 0220090059 (Other Identifier: IRB); 040807 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO