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

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)

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 2021

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

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)

Arms, Groups and Cohorts

  • Active Comparator: Surgery
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Rate of ductal carcinoma in situ (DCIS) pathologic complete response
    • Time Frame: 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 Measures

  • 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
    • 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 12 weeks
    • Rate of pathologic residual invasive carcinoma will be assessed in Arm 1 and Arm 2.

Participating in This Clinical Trial

Inclusion Criteria

  • Core needle biopsy demonstrating DCIS (ductal carcinoma in situ) of non-palpable, image-detected breast abnormality – Mammographic or MRI non-mass lesion (calcifications, non-mass enhancement on MRI) measuring 3 cm or less in greatest dimension – Estrogen receptor positive or negative, progesterone receptor positive or negative; HER2 positive or negative DCIS – 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. The post-biopsy mammogram must be performed within 6 weeks of randomization date – Placement of Savi scout optical reflectance marker for contouring of tumor bed area for partial breast irradiation treatment planning via mammography, CT, or MRI and for image-guiding of surgery – Planned lumpectomy. Mastectomy will be acceptable if lumpectomy fails by virtue of involved margins or size of lesion, or patient chooses this approach – Evaluation by Radiation Oncologist to ascertain feasibility of PBI prior to randomization. Planned breast irradiation should encompass less than 30% of the breast volume – Patients who had a prior contralateral invasive or non-invasive (DCIS) cancer are eligible – Eastern cooperative oncology group (ECOG) performance status 0, 1, or 2 Exclusion Criteria:
  • Invasive carcinoma on core needle biopsy, including microinvasive carcinoma – Radiographic extent of DCIS >3.0 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 dosimetric criteria for partial breast irradiation during radiation planning – 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
  • Gender Eligibility: Female

    Minimum Age: 18 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Stanford University
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Irene Wapnir, MD, Principal Investigator, Stanford University
    • Overall Contact(s)
      • Kathryn Bucknell, 650 723 0659, kaitlinz@stanford.edu

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