Phase 2 Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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A Randomized Phase 2 Study Comparing Surgical Excision Versus Neoadjuvant Radiotherapy Followed by Delayed Surgical Excision of Ductal Carcinoma In Situ (NORDIS)

Conditions
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Ductal Breast Carcinoma in Situ

Intervention / Treatment
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* Procedure: Lumpectomy
* Radiation: Partial breast irradiation prior to surgery


Participation Criteria
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Eligibility Criteria
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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 Mammographic or MRI non-mass lesion (calcifications, non-mass enhancement on MRI) measuring 4 cm or less in greatest dimension Estrogen receptor positive or negative, progesterone receptor positive or negative DCIS; HER2 positive, negative or unknown DCIS is allowed. Patients must have a biopsy marker placed within the tumor bed confirmed on post biopsy imaging and evidence of residual radiographic abnormality. The post-biopsy mammogram must be performed within 6 weeks of randomization date 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 landmarks are sufficient for radiation planning. If required, then placement occurs before treatment is initiated (surgery or neoRT), but not necessarily before randomization. If anatomic landmarks are used for arm 2, then needle or wireless devices are allowable for surgical preoperative targeting. 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 Review of imaging studies by 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 Protocol Version #9 19 March 18, 2021 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 Synchronous contralateral invasive or non-invasive 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 form meeting the study requirements or interfere with the interpretation of study results Endocrine therapy is not allowed prior to surgery unless continued for a contralateral cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgical Excision<br>Surgical excision of ductal carcinoma | Procedure: Lumpectomy<br>* Standard of Care surgery for DCIS (either lumpectomy or mastectomy)<br>* Other names: Mastectomy;|
| Experimental: Neoadjuvant partial breast irradiation<br>Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy. | Procedure: Lumpectomy<br>* Standard of Care surgery for DCIS (either lumpectomy or mastectomy)<br>* Other names: Mastectomy;Radiation: Partial breast irradiation prior to surgery<br>* Partial breast irradiation (PBI) will be delivered once aday for 5 days. The planned daily dose is 6 Gy prior to surgery (neo adjuvant)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ductal Breast Carcinoma