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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01208974
• Other study ID #: 20090299
• Secondary ID: SCCC-2009004
• Status: Recruiting
• Phase: N/A
• First received: September 22, 2010
• Last updated: March 28, 2018
• Start date: March 16, 2010
• Est. completion date: April 2021

Study information

• Verified date: March 2018
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Overall rationale: Prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction for patient with ductal carcinoma in-situ or invasive breast cancer will allow better cosmesis and patient's satisfaction:

• The use of NAC-sparing mastectomy followed by postoperative NAC (nipple-areola complex) external beam radiotherapy for selected patient with early stage invasive or in-situ breast cancers will be technically feasible and with acceptable complication rates.

• The cosmetic results after NAC-sparing mastectomy followed by postoperative external beam radiotherapy to the NAC will be better comparable with Skin Sparing Mastectomy.

• The local control rate in the NAC will be more than expected for a NAC sparing mastectomy without postoperative radiotherapy.

• The patient's satisfaction after NAC-sparing mastectomy followed by postoperative NAC external beam radiotherapy will be better than after Skin Sparing Mastectomy.

Description:

Study design: Phase I trial assessing the safety, feasibility and toxicity of prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction in patients with ductal carcinoma in-situ or invasive breast cancer.

Primary objective: To determine the recommended phase I dose of post-operative prophylactic NAC irradiation.

Secondary objectives: To provide extensive descriptive data regarding NAC-sparing surgery with reconstruction, including both surgeon experience and patient evaluation of cosmetic results. Survival and recurrence will be assessed.

Study size: Between 12 and 18 patients will be enrolled in the dose-escalation/deescalation part of this phase I study. An additional expansion cohort of 12 patients will be enrolled at the "potential" recommended phase II dose (RP2D) over an expected accrual period of 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2021
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma, Ductal
• Ductal Carcinoma

Intervention

Procedure:
• Nipple-Sparing Mastectomy
Subcutaneous Mastectomy (SCM) to be performed, preserving the nipple and areola complex, after a frozen section of the tissue underneath the nipple-areola complex is sampled and found to be negative for tumor. Performed during Week 1.
• Breast Reconstruction
Immediate reconstruction of the breast will be performed (after Nipple-Sparing Mastectomy) by the plastic surgeon, type depend on surgeon's discretion and patient's desire. Performed during Week 1.
• Axillary Surgery
Axillary Dissection or Sentinel Node Biopsy (SNB) will be performed at surgeon's discretion.

Radiation:
• Prophylactic Nipple-Areolar Complex RT
Prophylactic Nipple-Areolar Complex Radiation Therapy per protocol. Administered between weeks 5 to 8.

Locations

Country	Name	City	State
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the Recommended Phase II Dose (RP2D) of post-operative prophylactic NAC irradiation.	The recommended phase II dose will be the highest irradiation dose level at which <= 1 out of 6 study patients experiences dose-limiting toxicity (DLT). This dose will be the phase dose II of post-operative prophylactic NAC irradiation after NAC-sparing mastectomy with reconstruction in patients with ductal carcinoma in-situ or invasive breast cancer.	3-5 Years
Secondary	Surgery Success Rate	Surgery success rate, defined as the proportion of patients who had successful NAC sparing surgery with reconstruction divided by the total number of study patients, will be determined.	Up to 12 months
Secondary	Levels of Cosmetic Outcome in Study Participants - Number	Levels of cosmetic results will be assessed by both the physician(s) and the patients at 3, 6 and 12 months, using a 4-category ordinal scale (excellent, good, fair, and poor). Data will be summarized in terms of number of patients in these 4 possible categories at those assessment times separately for assessment by physician and by patient.	3, 6 and 12 months
Secondary	Levels of Cosmetic Outcome in Study Participants - Percentage	Levels of cosmetic results will be assessed by both the physician(s) and the patients at 3, 6 and 12 months, using a 4-category ordinal scale (excellent, good, fair, and poor). Data will be summarized in terms of percentage of patients in these 4 possible categories at those assessment times separately for assessment by physician and by patient.	3, 6 and 12 months
Secondary	Disease-Free Survival Rate in Study Participants	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.	Up to 5 years
Secondary	Overall Survival Rate in Study Participants	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..	Up to 5 years
Secondary	Recurrence Rate in Study Participants	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.	Up to 5 years