Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma

Ductal Breast Carcinoma in Situ Clinical Trial

— NORDIS  

Official title:

A Randomized Phase II Study Comparing Surgical Excision Versus Neoadjuvant Radiotherapy Followed by Delayed Surgical Excision of Ductal Carcinoma In Situ (NORDIS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03909282
• Other study ID #: IRB-46373
• Secondary ID: BRS0096NCI-2019-
• Status: Recruiting
• Phase: N/A
• Start date: March 22, 2019
• Est. completion date: July 2025

Study information

• Verified date: March 2024
• Source: Stanford University
• Contact: Sinyoung Park
• Phone: 650-721-4485
• Email: sinyoung[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this pilot study is to compare by pathological findings surgical excision versus neoadjuvant radiotherapy followed by delayed surgical excision of ductal carcinoma in situ (DCIS)

Description:

There will be measurable histopathological treatment effects identified in Arm 2 cases receiving pre-operative radiation. Results found are expected to assist in designing a more definitive study. Compare pathological findings in individuals with ductal carcinoma in situ (DCIS) who have surgical excision versus neoadjuvant radiotherapy followed by delayed surgical excision. It is noted that "phase 2" is formally associated with drug studies. Nonetheless, it is however part of the time of this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Core needle biopsy demonstrating DCIS (ductal carcinoma in situ) of non-palpable, image-detected breast abnormality
• Signed and dated IRB-approved written informed consent
• Women 18 years of age or older
• Mammographic calcifications or MRI non-mass enhancement measuring 4 cm or less in greatest dimension, including multifocal disease
• Estrogen receptor positive or negative, progesterone receptor positive or negative DCIS; HER2 positive, negative or unknown DCIS is allowed.
• Diagnostic needle biopsy within 16 weeks of randomization
• Patients must have a biopsy marker placed within the tumor bed confirmed on post biopsy imaging and evidence of residual radiographic abnormality. Confirmation of residual imaging abnormality is required within 6 weeks of randomization.
• Placement of Savi scout optical reflectance marker in tumor bed area as a wireless guide for surgery and for neoRT treatment planning is preferred but not required if anatomic metallic markers are sufficient for radiation planning. Placement does not have to occur before randomization. Additionally, wire localization before surgery is permissible.
• Planned lumpectomy. Mastectomy will be acceptable if lumpectomy fails by virtue of involved margins or size of lesion, or patient chooses this approach after randomization
• Radiation Oncologist to ascertain feasibility of PBI prior to randomization - based on their estimation that 30% or less of the breast volume will be encompassed in the radiation fields
• Patients who had a prior contralateral invasive or non-invasive (DCIS) cancer are eligible
• ECOG performance status 0, 1, or 2
• Concurrent foci of atypia or lobular carcinoma in situ in the ipsilateral or contralateral breast are allowed Exclusion Criteria
• Invasive carcinoma on core needle biopsy, including microinvasive carcinoma
• Radiographic extent of DCIS >4.0 cm
• Mass lesion on breast imaging or palpable tumor
• No residual radiographic lesion after diagnostic percutaneous core needle biopsy
• Prior history of ipsilateral invasive or noninvasive breast cancer
• Pregnant or breastfeeding
• Prior ipsilateral breast or chest irradiation
• Multicentric or multifocal DCIS, if extent is > 4cm
• Synchronous contralateral invasive or noninvasive breast cancer
• Pagets' disease of the breast
• Active collagen vascular disease
• Positive axillary lymph nodes
• Not meeting the described criteria for partial breast irradiation during initial clinical evaluation.
• Psychiatric or addictive disorders or other condition, that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with the interpretation of study results
• Endocrine therapy is not allowed from the time of study randomization to the completion of surgery unless the endocrine therapy is being continued for a contralateral cancer

Related Conditions & MeSH terms

• Breast Carcinoma In Situ
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Breast Carcinoma in Situ

Intervention

Procedure:
• Lumpectomy
Standard of Care surgery for DCIS (either lumpectomy or mastectomy)

Radiation:
• Partial breast irradiation prior to surgery
Partial breast irradiation (PBI) will be delivered once aday for 5 days. The planned daily dose is 6 Gy prior to surgery (neo adjuvant)

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of ductal carcinoma in situ (DCIS) pathologic complete response	A DCIS pathologic complete response will be defined as the absence of in situ carcinoma in the surgical resection specimen. The rate of DCIS pathologic complete response (pCR) will be calculated for Arm 1 and Arm 2.	12 weeks
Secondary	Correlation of ductal carcinoma in situ (DCIS) subtypes with rate of DCIS pathologic complete response to neoadjuvant partial breast irradiation (PBI)	Molecular subtypes based on gene expression profiling with therapy response will be corelated.; • DCIS subtypes will be defined based on grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status as follows: Low/intermediate grade versus high grade; ER/PR-negative versus ER/PR-positive; HER2-positive versus HER2-negative	12 weeks
Secondary	Tumor grade comparison of radiation-induced treatment effect pathologically pre- versus post-therapy	Tumor grade (grade 1, 2, 3) will be compared pre- and post-therapy.	12 weeks
Secondary	Nuclear atypia comparison of radiation-induced treatment effect pathologically pre- versus post-therapy	Degree of nuclear atypia (low, intermediate, high) will be compared pre- and post-therapy.	12 weeks
Secondary	Percent tumor necrosis comparison of radiation-induced treatment effect pathologically pre- versus post-therapy	Percent tumor necrosis (0-100%) will be quantified on the basis of percentage of overall residual tumor area and compared pre- and post-treatment.	12 weeks
Secondary	Tumor cellularity comparison of radiation-induced treatment effect pathologically pre- versus post-therapy	Tumor cellularity (0-100%) will be quantified on the basis of percentage of overall residual tumor area and compared pre- and post-treatment.	12 weeks
Secondary	Proportion of subjects experiencing a wound complication on Arm 1 compared to Arm 2	Wound complications and healing will be monitored in both arms.The following events will be considered wound complications: wound dehiscence, hematoma requiring intervention, seroma requiring drainage, skin necrosis requiring resection, cellulitis requiring antibiotic therapy.	12 weeks
Secondary	Correlation of post-radiation imaging characteristics with pathologic findings	Mammography obtained prior to surgical resection in Arm 2 patients will be assessed for the presence or absence of a residual mammographic abnormality, the size in mm of the residual mammographic abnormality and the longest span in mm of residual calcification and will be compared to the pathologic presence or absence of residual tumor, size in mm of the pathologic residual DCIS and whether the residual calcification is associated with pathologic residual DCIS.	12 weeks
Secondary	Rate of invasive carcinoma comparison in Arm 1 to Arm 2	Rate of pathologic residual invasive carcinoma will be assessed in Arm 1 and Arm 2.	12 weeks