Phase 2 Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma (NORDIS)
Primary Purpose
Ductal Breast Carcinoma in Situ
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Lumpectomy
Partial breast irradiation prior to surgery
Sponsored by
About this trial
This is an interventional treatment trial for Ductal Breast Carcinoma in Situ focused on measuring Ductal Breast Carcinoma
Eligibility Criteria
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
Sites / Locations
- Stanford UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Surgical Excision
Neoadjuvant partial breast irradiation
Arm Description
Surgical excision of ductal carcinoma
Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03909282
Brief Title
Phase 2 Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma
Acronym
NORDIS
Official Title
A Randomized Phase 2 Study Comparing Surgical Excision Versus Neoadjuvant Radiotherapy Followed by Delayed Surgical Excision of Ductal Carcinoma In Situ (NORDIS)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2019 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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)
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ductal Breast Carcinoma in Situ
Keywords
Ductal Breast Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Surgical Excision
Arm Type
Active Comparator
Arm Description
Surgical excision of ductal carcinoma
Arm Title
Neoadjuvant partial breast irradiation
Arm Type
Experimental
Arm Description
Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy.
Intervention Type
Procedure
Intervention Name(s)
Lumpectomy
Other Intervention Name(s)
Mastectomy
Intervention Description
Standard of Care surgery for DCIS (either lumpectomy or mastectomy)
Intervention Type
Radiation
Intervention Name(s)
Partial breast irradiation prior to surgery
Intervention Description
Partial breast irradiation (PBI) will be delivered once aday for 5 days. The planned daily dose is 6 Gy prior to surgery (neo adjuvant)
Primary Outcome Measure Information:
Title
Rate of ductal carcinoma in situ (DCIS) pathologic complete response
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Correlation of ductal carcinoma in situ (DCIS) subtypes with rate of DCIS pathologic complete response to neoadjuvant partial breast irradiation (PBI)
Description
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
Time Frame
12 weeks
Title
Tumor grade comparison of radiation-induced treatment effect pathologically pre- versus post-therapy
Description
Tumor grade (grade 1, 2, 3) will be compared pre- and post-therapy.
Time Frame
12 weeks
Title
Nuclear atypia comparison of radiation-induced treatment effect pathologically pre- versus post-therapy
Description
Degree of nuclear atypia (low, intermediate, high) will be compared pre- and post-therapy.
Time Frame
12 weeks
Title
Percent tumor necrosis comparison of radiation-induced treatment effect pathologically pre- versus post-therapy
Description
Percent tumor necrosis (0-100%) will be quantified on the basis of percentage of overall residual tumor area and compared pre- and post-treatment.
Time Frame
12 weeks
Title
Tumor cellularity comparison of radiation-induced treatment effect pathologically pre- versus post-therapy
Description
Tumor cellularity (0-100%) will be quantified on the basis of percentage of overall residual tumor area and compared pre- and post-treatment.
Time Frame
12 weeks
Title
Proportion of subjects experiencing a wound complication on Arm 1 compared to Arm 2
Description
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.
Time Frame
12 weeks
Title
Correlation of post-radiation imaging characteristics with pathologic findings
Description
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.
Time Frame
12 weeks
Title
Rate of invasive carcinoma comparison in Arm 1 to Arm 2
Description
Rate of pathologic residual invasive carcinoma will be assessed in Arm 1 and Arm 2.
Time Frame
12 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sinyoung Park
Phone
650-721-4485
Email
sinyoung@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene Wapnir, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sinyoung Park
Phone
650-721-4485
Email
sinyoung@stanford.edu
First Name & Middle Initial & Last Name & Degree
Irene Wapnir, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 2 Surgical Excision vs Neoadjuvant Radiotherapy+Delayed Surgical Excision of Ductal Carcinoma
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