Breast Cancer
Conditions
Brief summary
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.
Interventions
RADIATIONStereotactic body radiotherapy ( SBRT)
Single fraction of 21 Gy stereotactic radiotherapy (SBRT)delivered pre-operatively to subjects with early stage breast cancer
Sponsors
Duke University
Gateway for Cancer Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis | 6 months | Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome. |
| Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis. | 3 years | Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis | baseline | Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome. |
| Local Control in the Treated Breast Relative to Historic Controls | Through study completion estimated to be 10 years | Local control consists of annual clinical examination combined with breast imaging |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRachel Blitzblau, MD PhD
Duke Health
Participant flow
Recruitment details
Women ages 60 or older with clinically node-negative, 2cm or less, biopsy proven ductal carcinoma in situ or invasive carcinoma seen in the Duke Radiation Oncology department were considered for this trial. Women age 50-59 with a cT1N0 tumor and a low Oncotype score were also eligible.
Pre-assignment details
42 participants were withdrawn prior to starting study procedures due to insurance denial or ineligibility.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 41 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Patient reported rates of good/excellent cosmesis | 67 Participants |
| Physician reported rates of good/excellent cosmesis | 67 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 68 |
| other Total, other adverse events | 48 / 68 |
| serious Total, serious adverse events | 5 / 68 |
Outcome results
None listed