A Phase I Trial Assessing the Safety and Feasibility of Prophylactic Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Immediate Reconstruction in Patients With In-Situ or Invasive Breast Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Miami
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.
Study Overview
Brief Summary
The purpose of this research study is to see if a participant's nipple and areola can be safely preserved by adding radiation to these areas after a nipple-sparing mastectomy and immediate breast reconstruction.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have histologically confirmed in-situ or invasive breast carcinoma.
- •Tis, T1, T2 invasive or non-invasive carcinoma of the breast; lesion less than 4 cm.
- •Unifocal, multifocal or multicentric breast cancers that can be removed by nipple sparing mastectomy with negative surgical margins.
- •No extensive intraductal component or patient with distant metastases.
- •Patients must be > 18 years of age.
- •No concomitant or history of nipple discharge or skin involvement.
- •No prior history of malignancy (less than 5 years prior to study entry), except non-melanomatous skin cancer.
- •No prior history of radiation to the chest.
- •No collagenous disease (systemic lupus erythematosis, scleroderma, dermatomyositis)No previous non-hormonal therapy including radiation or chemotherapy for current breast cancer.
- •No patients with Paget's disease of the nipple.
- •No patients with co-existing medical conditions with life expectancy < 2 years.
- •No pregnant or lactating women.
- •Eastern Cooperative Oncology Group (ECOG) 0 -
- •Signed study-specific informed consent form prior to the study entry.
Exclusion Criteria
- •Retroareolar breast cancer lesions within one cm, depth from the skin surface.
- •Concomitant or history of nipple discharge or skin involvement.
- •Patient with distant metastases.
- •Patient with extensive intraductal carcinoma.
- •Any previously irradiated ipsilateral breast cancer.
- •Patients with Paget's disease of the nipple.
- •Patients with collagenous diseases, as systemic lupus erythematosis, scleroderma or dermatomyositis.
- •Other malignancy, except nonmelanomatous skin cancer, less than 5 years prior to participation in this study.
- •Patients who are pregnant or lactating due to potential exposure of the fetus to RT and unknown effects of RT to lactating females.
- •Positive surgical margins following nipple sparing mastectomy.
Arms & Interventions
Phase 1 MTD NAC RT
Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:
- Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
- Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
- Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
- Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy
Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).
Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.
Intervention: Nipple-Sparing Mastectomy (Procedure)
Phase 1 MTD NAC RT
Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:
- Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
- Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
- Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
- Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy
Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).
Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.
Intervention: Axillary Surgery (Procedure)
Phase 1 MTD NAC RT
Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:
- Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
- Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
- Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
- Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy
Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).
Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.
Intervention: Prophylactic Nipple-Areolar Complex RT (Radiation)
Phase 1 MTD NAC RT
Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:
- Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
- Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
- Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
- Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy
Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).
Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.
Intervention: Breast Reconstruction (Procedure)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.
Time Frame: Up to 13 weeks
The recommended Phase II dose will be reported as the MTD at which only 0 or 1 out of 6 participants experiences dose limiting toxicity (DLT). DLT will be reported as any of the following: Grade 4 skin rash or pain, NAC necrosis, any toxicity requiring interruption of NAC irradiation greater than 2 weeks or any grade 4 or 5 treatment related toxicity. Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.
Secondary Outcomes
- Cosmetic Outcome(12 months)
- Disease-Free Survival Rate in Study Participants(Up to 5 years)
- Overall Survival Rate in Study Participants(Up to 5 years)
- Recurrence Rate in Study Participants(Up to 5 years)
Investigators
Cristiane Takita
Professor of Clinical
University of Miami