Repeat Breast Conserving Surgery Followed by Daily Partial Breast Irradiation in Ipsilateral Breast

Repeat Breast Conserving Surgery Followed by Daily Partial Breast Irradiation for Participants With Ipsilateral Breast Tumor Recurrence Treated Initially With Breast Conserving Surgery and Whole Breast Radiation Therapy

The standard treatment for participants whose cancer has returned after breast conserving surgery is radiation given twice daily (separated by at least 6 hours) for a total of 30 treatments. The purpose of this study is to find out if giving radiation once a day for 15 treatments after repeat breast conserving surgery works as well as giving it the standard way.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Tumor, Breast
• Intervention / Treatment: Radiation: Radiation Therapy

Detailed Description

Breast cancer survival rates have greatly improved with advances in both screening and treatment. The standard of care for both early stage and selected locally advanced breast cancers is breast conserving therapy (BCT), consisting of a partial mastectomy followed by radiation treatment. Traditionally, a salvage mastectomy was the standard treatment for women who initially underwent BCT and experienced an ipsilateral breast tumor recurrence (IBTR). Many participants have become increasingly motivated to avoid mastectomy, and there has been rising interest in repeat BCS (Breast Conserving Surgery) with focal radiation for certain participants motivated to keep their breast. The current standard of care for breast re-irradiation after an in-breast tumor recurrence is partial breast irradiation consisting of a dose of 45 Gy delivered BID for 30 fractions. While this regimen demonstrated excellent local control and low AEs, the regimen itself is difficult for participants. Receiving RT twice daily at smaller doses per fraction (1.5 Gy) for 30 treatments can be burdensome, especially for those without reliable transportation or difficulty getting time away from work. Given the excellent local control rates and low rate of AEs, in this study, we hypothesize that daily hypofractionated EBRT(External Beam Radiation Therapy) for re-irradiation after repeat BCS would be at least as well tolerated with good local control and provide a more convenient option for participants than the current standard of care established by RTOG 1014. Some participants will present with high-risk features (e.g. age <50, high grade, ER negative tumors, close margins) making dose escalation an attractive option to improve local control. Options for dose escalation include sequential and concurrent administration of a boost.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Janice Lyons, MD; Phone Number: (216) 844-2514; Email: Janice.lyons@uhhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
      • Contact: Rahul Tendulkar, MD; Phone Number: 866-223-8100; Email: TaussigResearch@ccf.org
      • Principal Investigator: Rahul Tendulkar, MD
    • Cleveland, Ohio, United States, 44106-5065
      • Recruiting
      • University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants' recurrences must have histologically confirmed ductal carcinoma in-situ, invasive ductal, medullary, papillary, colloid (mucinous), tubular or mixed histologies. Three years of time must have elapsed since the end of the last course of whole breast irradiation.
• Lesion size < 3 cm treated with a partial mastectomy. Participants with invasive cancer and clinically and radiographically negative axillas do not require an axillary lymph node sampling unless they did not have prior axillary lymph node sampling (e.g. previous cancer was DCIS). Participants with DCIS as their recurrence do not require surgical assessment of the axilla. Repeat sentinel lymph node biopsy is permitted.
• Negative resection margins with at least no tumor on ink or a negative re-excision.
• Participants with invasive recurrence must have a negative re-staging work-up consisting of either a CT chest/abdomen and a bone scan or a PET scan.
• Hormonal therapy is allowed. If chemotherapy is planned, it can be delivered either prior to or after the radiation is delivered. There must be at least 2 weeks between radiation and chemotherapy. HER2 directed therapy can be delivered concurrently with radiation.
• Participants must be > 18 years of age. Because no dosing or adverse event data are currently available on the use of breast re-irradiation in participants ≤18 years of age, children are excluded from this study.
• Participants must have the ability to understand and the willingness to sign a written informed consent document.
• Performance status: ECOG Performance status ≤ 2.
• Life expectancy of ≥ 12months, in the opinion of and as documented by the investigator.
• Not based on gender; this trial is open to any gender, defined as self-representation of gender identity.

Exclusion Criteria:

• Participants with nodal or distant metastatic disease < 3 years since prior radiation.
• Participants with invasive pure lobular carcinoma, extensive lobular carcinoma in-situ, extensive ductal carcinoma in-situ (spanning more than 3 cm), or uncontrolled nonepithelial breast malignancies such as lymphoma or sarcoma.
• Participants with multicentric carcinoma (tumors in different quadrants of the breast or tumors separated by at least 4 cm). Palpable or radiographically suspicious contralateral axillary, ipsilateral or contralateral supraclavicular, infraclavicular, or internal mammary lymph nodes unless these are histologically or cytologically confirmed negative.
• Participants with Paget's disease of the nipple.
• Participants with skin involvement.
• Participants with scleroderma or dermatomyositis.
• Participants with psychiatric, neurologic, or addictive disorders that would preclude obtaining informed consent.
• Participants who are pregnant or lactating due to potential fetal exposure to radiation and unknown effects of radiation on lactating females.
• Participants with known BRCA 1/BRCA 2 mutations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiation Therapy(RT); There will be one treatment cohort. Radiation therapy will be delivered daily for 15 daily fractions, 2.67Gy per fraction, delivered using a 3-D or IMRT(Intensity Modulate Radiation Therapy) plan. For participants with high-risk features deemed by the radiation oncologist who would otherwise be a candidate for a boost (age <50, high grade, poor biology, close margins), 48 Gy delivered in fifteen fractions of 3.2 Gy is allowed.

Radiation: Radiation Therapy; Weeks 1, 2 and 3; Weeks 1, 2 and 3 will include 5 days of treatment.; One radiation treatment to breast on each of the 5 days. Each radiation treatment session will last a 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events as graded by CTCAE criteria	Rate of grade 3+ treatment-related skin, fibrosis, and breast pain adverse events occurring within 1 year from the completion of re-irradiation as graded by CTCAE criteria.	1 year from the completion of re-irradiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-breast tumor recurrence rate	The overall in-breast tumor recurrence rate will be estimated using the cumulative incidence function.	3 years
In-breast tumor recurrence rate	The overall in-breast tumor recurrence rate is estimated using the cumulative incidence function.	5 years
In-breast tumor recurrence rate	The overall in-breast tumor recurrence rate will be estimated using the cumulative incidence function.	10 years
Rate of freedom from mastectomy	The freedom from mastectomy rate will be estimated using the cumulative incidence function.	3 years
Rate of freedom from mastectomy	The freedom from mastectomy rate will be estimated using the cumulative incidence function.	5 years
Rate of freedom from mastectomy	The freedom from mastectomy rate will be estimated using the cumulative incidence function.	10 years
Treatment-related adverse events	All treatment-related adverse events for the defined time periods	1 year from completion of re-irradiation
Treatment-related adverse events	All treatment-related adverse events for the defined time periods	Overall for 3 years from completion of re-irradiation
Evaluation of Cosmesis	Determined by an established Global Cosmesis Score grading from 1 through 4, with 1 being excellent and 4 being rated as poor	1 year
Evaluation of Cosmesis	Determined by an established Global Cosmesis Score grading from 1 through 4, with 1 being excellent and 4 being rated as poor	3 years
Overall survival rate	Overall survival will be estimated using Kaplan-Meier Method	3 years
Overall survival rate	Overall survival will be estimated using Kaplan-Meier Method	5 years
Overall survival rate	Overall survival will be estimated using Kaplan-Meier Method	10 years
Mastectomy-free survival rate	Mastectomy-free survival will be estimated using Kaplan-Meier Method	3 years
Mastectomy-free survival rate	Mastectomy-free survival will be estimated using Kaplan-Meier Method	5 years
Mastectomy-free survival rate	Mastectomy-free survival will be estimated using Kaplan-Meier Method	10 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Janice Lyons, MD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center; Principal Investigator: Rahul Tendulkar, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Estimated): August 9, 2029
• Study Completion (Estimated): August 9, 2029

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiation Therapy; Tumor; Re-irradiation; In-Breast Recurrence
• Additional Relevant MeSH Terms: Neoplasms by Site; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Neoplasms; Breast Neoplasms; Therapeutics; Radiotherapy
• Other Study ID Numbers: CASE4123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be used for study purposes only and not otherwise shared

Drug and device information, study documents

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