Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction

Not Applicable

Active, not recruiting

Conditions: Breast Cancer
Ductal Carcinoma

Interventions: Procedure: Nipple-Sparing Mastectomy
Procedure: Breast Reconstruction
Procedure: Axillary Surgery
Radiation: Prophylactic Nipple-Areolar Complex RT

Registration Number: NCT01208974

Lead Sponsor: University of Miami

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Female

Target Recruitment: 21

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 - 2.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1 MTD NAC RT	Nipple-Sparing Mastectomy	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.
Phase 1 MTD NAC RT	Axillary Surgery	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.
Phase 1 MTD NAC RT	Breast Reconstruction	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.
Phase 1 MTD NAC RT	Prophylactic Nipple-Areolar Complex 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.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.	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 Outcome Measures

Name	Time	Method
Disease-Free Survival Rate in Study Participants	Up to 5 years	Disease-free survival rate in study participants will be assessed. Disease-free survival is defined from the date of surgery until the date of documented recurrence (local or distant) or breast cancer-related death, whichever occurs first. Patients who die without documentation of recurrence will be considered to have had disease recurrence at the time of death, unless there is documented evidence that no recurrence occurred before death.
Overall Survival Rate in Study Participants	Up to 5 years	Overall Survival rate in study participants will be assessed. Overall survival is the defined from the date of surgery until the date of death due to any cause. In the absence of death, follow-up time will be censored by the date of last contact..
Cosmetic Outcome	12 months	Cosmetic Outcome will be reported as the number of participants in each of the 4 cosmetic outcome category ordinal scale. The 4 cosmetic outcome category scales are excellent, good, fair and poor. Both physician and patient's evaluation will be reported.
Recurrence Rate in Study Participants	Up to 5 years	Rate of disease recurrence in study participants. The definition of local recurrence is histologic evidence of recurrent carcinoma, either invasive or non-invasive in the nipple-areola complex in the ipsilateral breast. Clinical evidence of carcinoma by physical exam and/or mammograms/MRI will not be evidence of local recurrence until biopsy proof.