Trial to Compare Radiation Fibrosis With Five Versus Three Fractions

Prone Partial Breast Irradiation (PBI): Prospective Randomized Controlled Non-inferiority Trial to Compare Radiation Fibrosis With Five Versus Three Fractions

Post meno-pausal women with T1 Breast cancers will be randomized to receive either 600 centiGray (cGy) X 5 over five consecutive days (arm 1) versus 800 cGy X 3 fractions given every other day (arm 2). Patients will complete treatment in one week. All patients will be followed a month after the completion of treatment then q6 months for the first year, then yearly for the next 10 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Neoplasm of Breast Stage I
• Intervention / Treatment: Radiation: Arm 1 600 cGY x 5 fractions; Radiation: Arm 2 800 cGY x 3 fractions

Detailed Description

Partial breast irradiation (PBI) is becoming a new paradigm for breast cancer radiation. No type I or II evidence is currently available to demonstrate equivalence to standard whole breast radiotherapy, and a prospective randomized trial jointly sponsored by NSABP and Radiation therapy Oncology Group (RTOG) (NSABP B-39 and RTOG 0413) has completed accruing patients, comparing whole breast radiotherapy to PBI, either by brachytherapy or external beam techniques (EB): results of this trial are pending. Until results of this or similar trials are available, PBI remains a research domain, and it should be offered to patients only in the context of a clinical experimental protocol. Despite the fact that less extensive experience than that of brachytherapy is available, PBI delivery through an external-beam has many advantages. First of all, it is likely to be more acceptable to the patient since it is non-invasive and it does not require a surgical procedure or anesthesia. Moreover, since it is delivered after surgery, the pathological analysis of the segmental mastectomy specimen is available to inform the selection of the best candidates. In addition, EB-PBI is likely to become more widely reproducible, since it does not rely on the experience and skills of the radiation oncologist performing the brachytherapy implant. Besides, once the technique is established, it can be widely applied at any facility provided with a linear accelerator, without the risk presented by some brachytherapy approaches that cannot be completed because of the unfavorable interplay of patient's anatomy with the technical limitations of the applicator. Finally, in terms of health care economics, an external beam approach spares the costs of an extra surgical procedure and several days as inpatient (in the case of Low dose Rate (LDR) brachytherapy).

A prone approach for partial breast radiation has been tested at NYU in a clinical trial sponsored by an IDEA grant of the Department of Defense (NYU 00-23). Results of the first 47 patient accrued originally demonstrated feasibility. Eligibility to this study was limited to post-menopausal women with non-palpable, mammographically detected tumors. In addition, the protocol required patients to have first refused to undergo standard six-week radiotherapy. Five fractions of 6 Gy were delivered to the Planning Target Volume (PTV) over ten days (Monday-Wednesday-Friday, Monday-Wednesday). The dose and fractionation was based on radiobiological modeling, aimed at determining a dose to deliver in five fractions that would achieve equivalence to the tumor control estimates of 50 Gy in 25 fractions, while maintaining a risk of fibrosis at the tumor bed comparable to that of a standard regimen of 60 Gy in 30 fractions. An α/β = 4 for tumor control was used, and its validity has been recently confirmed by the results of a prospective randomized trial comparing accelerated to standard whole breast radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 11215
      • Brooklyn Methodist Hospital - NewYork Presbyterian
    • New York, New York, United States, 11355
      • New York Presbyterian Hospital - Queens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Post-menopausal women with status post segmental mastectomy defined as either 1) at least 2 years without menstrual period or 2) or patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with Follicle Stimulating Hormone (FSH) confirmation of post-menopausal status.
2. Stage 1 (pT1) breast cancer, excised with negative margins.
3. clinically N0 or No Regional Lymph node (pN0) or sentinel node negative

Exclusion Criteria:

1. Previous radiation therapy to the ipsilateral breast.
2. Presence of a proportion of Ductal Carcinoma in-situ (DCIS) in the core biopsy specimen which is compatible with extensive intraductal component (EIC).

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
Other: Arm 1 - 600 cGY x 5 fractions; Patients will receive 600 cGY x 5 fractions of radiation therapy over 5 consecutive days.	Radiation: Arm 1 600 cGY x 5 fractions; Patients who are randomized to Arm 1 will receive either 600 cGY x 5 fractions over 5 consecutive days
Other: Arm 2 - 800 cGY x 3 fractions; Patients will receive 800 cGY x 3 fractions of radiation therapy every other day for 3 days.	Radiation: Arm 2 800 cGY x 3 fractions; Patients who are randomized to Arm 2 will receive 800 cGY x 3 fractions given every other day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with grade 2 or 3 fibrosis between the two treatment groups will be compared.	The primary analysis will be the difference in proportions of patients with grade 2 or 3 fibrosis between the two treatment groups compared using a non-inferiority z- test. The proportions of patients by grade of fibrosis will be compared in the two treatment arms using contingency table methods and chi square tests.	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rates will be documented	Rates of recurrence at 1, 2, and 3 years post-randomization will be estimated with 95% confidence limits within treatment groups along with plots of Kaplan-Meier time to recurrence curves	60 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Silvia C Formenti, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2015
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: April 28, 2016
• First Posted (Estimated): April 29, 2016

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 1505016201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data and medical information obtained will be kept confidential to the extent permitted by law and will not be released without the patient's written permission except as described in this paragraph. In all study forms, patients will be identified only by their initials and patient number. Patient names will not be reported in any publication; only the data obtained as a result of their participation in this study will be made public.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes