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

Official title

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

Overview

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.

Interventions

• 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)

Primary outcome measures

• Rate of ductal carcinoma in situ (DCIS) pathologic complete response [Time frame: 12 weeks]

Secondary outcome measures (8)

• Correlation of ductal carcinoma in situ (DCIS) subtypes with rate of DCIS pathologic complete response to neoadjuvant partial breast irradiation (PBI) [Time frame: 12 weeks]
• Tumor grade comparison of radiation-induced treatment effect pathologically pre- versus post-therapy [Time frame: 12 weeks]
• Nuclear atypia comparison of radiation-induced treatment effect pathologically pre- versus post-therapy [Time frame: 12 weeks]
• Percent tumor necrosis comparison of radiation-induced treatment effect pathologically pre- versus post-therapy [Time frame: 12 weeks]
• Tumor cellularity comparison of radiation-induced treatment effect pathologically pre- versus post-therapy [Time frame: 12 weeks]
• Proportion of subjects experiencing a wound complication on Arm 1 compared to Arm 2 [Time frame: 12 weeks]
• Correlation of post-radiation imaging characteristics with pathologic findings [Time frame: 12 weeks]
• Rate of invasive carcinoma comparison in Arm 1 to Arm 2 [Time frame: 12 weeks]

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
• 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, negative or unknown; 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.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Stanford University — Stanford

Identifiers

NCT: NCT03909282 · IRB-46373 · BRS0096 · NCI-2019-02516

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗