Study of Preoperative Boost Radiotherapy

A Phase II Study of Preoperative Boost Radiotherapy in Patients With Breast With Biomarker Analysis

This protocol seeks to utilize a novel method of tumor bed boost delivery and to better understand breast cancer radiation response through the analysis of pre-and post-radiation breast tumor samples.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Single fraction of 7 Gy

Detailed Description

The study team proposes in this trial to build on the favorable results of the intraoperative boost trials but using a preoperative delivery approach. The PI has demonstrated the feasibility of the preoperative approach and successfully completed a Phase I dose-finding partial breast trial. The preoperative approach has several advantages: 1) expensive intra-operative equipment is unnecessary, 2) a small intact breast tumor results in significantly less uninvolved breast tissue receiving high radiation doses which likely decreases toxicity; 3) more accurate targeting of the high-risk areas of subclinical disease surrounding the tumor is possible, 4) smaller treatment volumes are amenable to dose escalation which can further accelerate treatment and improve accessibility for subjects, and 5) the pre-operative approach provides a novel opportunity to study breast cancer radiation response.

Radiotherapy to the intact tumor is a relatively rare event in breast cancer irradiation, particularly in the setting of early stage breast cancer. Tumor and normal tissue radiation response remain relatively poorly understood. Markers capable of predicting radiation response are rare indeed. Therefore, paired pre- and post-radiation tissue will be examined for FAS gene expression and compared among the breast cancer subtypes. FAS is the name of a gene ( not an acronym) that is known to play a critical role in the induction of programmed cell death and is an established prognostic marker in breast cancer. Previous study team findings that FAS induction appears to be breast cancer subtype-specific has not been previously observed and provides a possible explanation for the differential rates of tumor response observed clinically in distinct breast tumor subtypes. The study team's preclinical work with FAS suggests a potential role as a radiation response biomarker. The study goal is to validate those findings in this large cohort of diverse breast cancer subjects. However, because preoperative delivery of the boost to the intact tumor is unique, this study will include a secondary cosmetic outcome that includes predefined stopping boundaries for early indications of suboptimal cosmetic outcomes with this novel approach

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma of the breast. Biopsy tissue (either slides or block) from outside institutions will be reviewed to confirm diagnosis.
2. Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging evidence of multicentric disease preventing resection through a single incision, no pregnant women, and no comorbid conditions precluding surgery)
3. cTis-T3 cancer judged to benefit (by treating radiation oncologist) from a tumor bed boost
4. Women of child-bearing potential must consent to use adequate contraception during the course of the study: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use.
5. White blood cell (WBC) > 3000, Hgb > 10, platelets >100000 within 30 days of consent
6. Eligible for contrasted magnetic resonance imaging( MRI) on initial evaluation with glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within 60 days of diagnosis will be considered an acceptable alternative and will not be repeated.
7. Outside breast imaging will be reviewed at Duke to confirm that findings are consistent with trial eligibility

Exclusion Criteria:

1. Breast implant in the breast to be treated (contralateral breast implant is acceptable)
2. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus, rheumatoid arthritis, scleroderma)
3. Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach for at least 1 hour
4. Positive serum pregnancy test
5. Insufficient breast imaging to judge clinical stage
6. Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement.
7. Subjects in whom treatment planning constraints cannot be met

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: Single arm 7 Gray (Gy) fraction of radiotherapy; All subjects will receive a single 7 Gy fraction of radiotherapy to the intact tumor prior to surgery.	Radiation: Single fraction of 7 Gy; All subjects will receive a single 7 Gy fraction of radiotherapy to the intact tumor prior to surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cosmesis Evaluations Using the NRG Oncology Cosmesis Scale	Change from baseline rates of cosmesis at 3 years post-treatment as measured by the NRG Oncology cosmesis scale. The scale is scored from 1 (excellent) to 4 (poor) with a lower number representing better physical appearance.	baseline to 3 years post radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Circulating Cell Free DNA to Identify Potential Radiation Response Biomarkers	Blood collected pre and post treatment will be used to explore the biologic response to radiotherapy by comparing changes in circulating cell-free DNA expression pre and post-radiotherapy:	5 years
Quality of Life as Measured by Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire	Patient-reported Quality of Life as measured by the Functional Assessment of Cancer Therapy - Breast (FACT-B) at 3 years post-treatment. The FACT-B includes 35 items scored on a Likert-type scale from 0 (not at all) to 4 (very much) with a total scale range of 0-140 and a lower total score indicating a better outcome. Only the total scale score is reported; subscales scores are not reported.	3 years
Composite Review of Local Control	Document local control in the treated breast relative to historical controls with annual clinical exam and imaging studies. Local control is defined as the time from start of treatment to date of local recurrence estimated using the Kaplan-Meier method.	5-10 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Gateway for Cancer Research
• Investigators: Principal Investigator: Rachel Blitzblau, MD PhD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2015
• Primary Completion (Actual): June 25, 2021
• Study Completion (Actual): June 25, 2021

Study Registration Dates

• First Submitted: June 22, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: Pro00063936

Drug and device information, study documents

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