Description:
This protocol seeks to build on the favorable results of the investigators' phase I trial
(Pro00015617) by extending the findings to a larger cohort of subjects.In this study, the
investigators hypothesize that 21Gy (Gray) as a single fraction can be delivered
preoperatively to a larger group of subjects (n100).
The primary objective is to determine physician reported rates of good/excellent cosmesis at
baseline and 6 months, 1, 2, and 3 years post-treatment as measured by the NRG cosmesis scale
Title
- Brief Title: Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer
- Official Title: A Phase II Preoperative Single-Fraction Partial Breast Radiotherapy in Early Stage Breast Cancer: Analysis of Pathologic Response
Clinical Trial IDs
- ORG STUDY ID:
Pro00063848
- NCT ID:
NCT02482376
Conditions
Purpose
This protocol seeks to build on the favorable results of the investigators' phase I trial
(Pro00015617) by extending the findings to a larger cohort of subjects.In this study, the
investigators hypothesize that 21Gy (Gray) as a single fraction can be delivered
preoperatively to a larger group of subjects (n100).
The primary objective is to determine physician reported rates of good/excellent cosmesis at
baseline and 6 months, 1, 2, and 3 years post-treatment as measured by the NRG cosmesis scale
Detailed Description
The study team hypothesizes that a single fraction of 21Gy can be delivered preoperatively to
the intact breast tumor with acceptable cosmetic outcomes. Furthermore, the investigators
anticipate that pre- and post-radiation breast tumor samples will provide an avenue for
understanding breast cancer radiation response
Rationale for single-fraction preoperative technique
This trial is proposed to build on the favorable results of the investigators' phase I trial
by extending the findings to a larger cohort of subjects. The preoperative approach has
several advantages:
1. a small intact breast tumor results in significantly less uninvolved breast tissue
receiving high radiation doses which likely decreases toxicity;
2. more accurate targeting of the high-risk areas of subclinical disease surrounding the
tumor is possible,
3. smaller treatment volumes are amenable to dose escalation which can further accelerate
treatment and improve accessibility for subjects,
4. this technical approach is widely utilized in other tumor sites and can be delivered at
most radiation facilities
5. the pre-operative approach provides a novel opportunity to study breast cancer radiation
response.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Single arm 21Gy stereotactic radiotherapy | Other | Subjects will receive a single fraction of 21Gy of stereotactic radiotherapy before proceeding to surgery. | |
Eligibility Criteria
Inclusion Criteria:
1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma
of the breast
a. 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 or multifocal disease, no pregnant women, and no comorbid
conditions precluding surgery)
3. Clinical T1N0M0 invasive carcinoma or Ductal carcinoma in situ (DCIS) < or equal to
2cm
4. 60 years of age or older or 50-59 with a low Oncotype score (0-17) Oncotype is not
required for women diagnosed with DCIS.
5. Estrogen receptor positive (ER+), Human epidermal growth factor 2 negative (HER2-)
HER-2 status is not required for women diagnosed with DCIS.
6. Women of child-bearing potential must consent to use adequate contraception during the
course of the study. Female subjects must agree to use a medically acceptable
contraceptives including: (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.
7. White blood cells (WBC) > 3000, Hemoglobin ( Hgb) > 9, platelets >100000 within 30
days of consent
8. Eligible for contrasted magnetic resonance imaging (MRI) on initial evaluation with
glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within one
month will be considered an acceptable alternative and will not be repeated.
9. Outside breast imaging will be reviewed at Duke to confirm findings are consistent
with trial eligibility.
Exclusion Criteria:
1. Neoadjuvant chemotherapy
2. Breast implant in the breast to be treated with SBRT
3. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus,
rheumatoid arthritis, scleroderma)
4. Subjects unable to receive study treatment planning secondary to body habitus or
inability to lie flat on the stomach at length
5. HER2 positive
6. Positive serum pregnancy test
7. Insufficient breast imaging to judge clinical stage
8. Subjects without placement of a biopsy clip at the diagnostic procedure who are
unwilling to undergo clip placement.
9. Subjects in whom treatment planning constraints cannot be met
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 50 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Physician reported rates of good/excellent cosmesis. |
| Time Frame: | Through study completion estimated to be 3 years |
| Safety Issue: | |
| Description: | Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points |
Secondary Outcome Measures
| Measure: | Ki-67 will be assessed as a measure of tumor response |
| Time Frame: | Through study completion estimated to be 3 years |
| Safety Issue: | |
| Description: | Ki-67 will be assessed in the pre and post radiotherapy tissue samples |
| Measure: | Patient reported rates of good/excellent cosmesis |
| Time Frame: | Through study completion estimated to be 3 years |
| Safety Issue: | |
| Description: | Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints |
| Measure: | The impact of radiation on gene expression |
| Time Frame: | Through study completion estimated to be 3 years |
| Safety Issue: | |
| Description: | Gene expression will be assessed using the Affymetrix Human Transcriptome Array (HTA) arrays designed for formalin fixed paraffin embedded (FFPE) samples on pre and post radiation therapy tissue samples. |
| Measure: | Local control in the treated breast relative to historic controls |
| Time Frame: | Through study completion estimated to be 5-10 years |
| Safety Issue: | |
| Description: | Annual clinical examination combined with breast imaging |
| Measure: | Assess the impact of RT on circulating cell free DNA |
| Time Frame: | Through study completion estimated to be 3 years |
| Safety Issue: | |
| Description: | Oxidative stress biomarkers will be measured in serum and urine collected at the same timepoints |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Duke University |
Last Updated
May 28, 2021
