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

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03909282

Collaborator

(none)

Enrollment

Location

Arms

75.3

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Ductal Breast Carcinoma in Situ	Procedure: Lumpectomy Radiation: Partial breast irradiation prior to surgery	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 22, 2019

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Surgical Excision Surgical excision of ductal carcinoma	Procedure: Lumpectomy Standard of Care surgery for DCIS (either lumpectomy or mastectomy) Other Names: Mastectomy
Experimental: Neoadjuvant partial breast irradiation Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy.	Procedure: Lumpectomy Standard of Care surgery for DCIS (either lumpectomy or mastectomy) Other Names: 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)

Arm

Intervention/Treatment

Active Comparator: Surgical Excision

Surgical excision of ductal carcinoma

Procedure: Lumpectomy

Standard of Care surgery for DCIS (either lumpectomy or mastectomy)

Other Names:

Mastectomy

Experimental: Neoadjuvant partial breast irradiation

Partial breast irradiation will be delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy.

Procedure: Lumpectomy

Standard of Care surgery for DCIS (either lumpectomy or mastectomy)

Other Names:

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)

Outcome Measures

Primary Outcome Measures

Rate of ductal carcinoma in situ (DCIS) pathologic complete response [12 weeks]
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) [12 weeks]
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 [12 weeks]
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 [12 weeks]
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 [12 weeks]
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 [12 weeks]
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 [12 weeks]
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 [12 weeks]
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 [12 weeks]
Rate of pathologic residual invasive carcinoma will be assessed in Arm 1 and Arm 2.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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