Clinical trial NCT02482389: Study of Preoperative Boost Radiotherapy
Official title: A Phase II Study of Preoperative Boost Radiotherapy in Patients With Breast With Biomarker Analysis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Breast Cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Gateway for Cancer Research
First posted: 2015-06-26
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Cosmesis Evaluations Using the NRG Oncology Cosmesis Scale
timeFrame: baseline to 3 years post radiation therapy
Secondary outcomes:
measure: Change Circulating Cell Free DNA to Identify Potential Radiation Response Biomarkers
timeFrame: 5 years
measure: Quality of Life as Measured by Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire
timeFrame: 3 years
measure: Composite Review of Local Control
timeFrame: 5-10 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Health
name: Rachel Blitzblau, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: