Clinical Trials /

Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer

NCT02482376

Description:

This protocol seeks to build on the favorable results of the investigators' phase I trial (Pro00015617) by extending the findings to a larger cohort of subjects.In this study, the investigators hypothesize that 21Gy (Gray) as a single fraction can be delivered preoperatively to a larger group of subjects (n100). The primary objective is to determine physician reported rates of good/excellent cosmesis at baseline and 6 months, 1, 2, and 3 years post-treatment as measured by the NRG cosmesis scale

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer
  • Official Title: A Phase II Preoperative Single-Fraction Partial Breast Radiotherapy in Early Stage Breast Cancer: Analysis of Pathologic Response

Clinical Trial IDs

  • ORG STUDY ID: Pro00063848
  • NCT ID: NCT02482376

Conditions

  • Breast Cancer

Purpose

This protocol seeks to build on the favorable results of the investigators' phase I trial (Pro00015617) by extending the findings to a larger cohort of subjects.In this study, the investigators hypothesize that 21Gy (Gray) as a single fraction can be delivered preoperatively to a larger group of subjects (n100). The primary objective is to determine physician reported rates of good/excellent cosmesis at baseline and 6 months, 1, 2, and 3 years post-treatment as measured by the NRG cosmesis scale

Detailed Description

      The study team hypothesizes that a single fraction of 21Gy can be delivered preoperatively to
      the intact breast tumor with acceptable cosmetic outcomes. Furthermore, the investigators
      anticipate that pre- and post-radiation breast tumor samples will provide an avenue for
      understanding breast cancer radiation response

      Rationale for single-fraction preoperative technique

      This trial is proposed to build on the favorable results of the investigators' phase I trial
      by extending the findings to a larger cohort of subjects. The preoperative approach has
      several advantages:

        1. a small intact breast tumor results in significantly less uninvolved breast tissue
           receiving high radiation doses which likely decreases toxicity;

        2. more accurate targeting of the high-risk areas of subclinical disease surrounding the
           tumor is possible,

        3. smaller treatment volumes are amenable to dose escalation which can further accelerate
           treatment and improve accessibility for subjects,

        4. this technical approach is widely utilized in other tumor sites and can be delivered at
           most radiation facilities

        5. the pre-operative approach provides a novel opportunity to study breast cancer radiation
           response.
    

Trial Arms

NameTypeDescriptionInterventions
Single arm 21Gy stereotactic radiotherapyOtherSubjects will receive a single fraction of 21Gy of stereotactic radiotherapy before proceeding to surgery.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma
                 of the breast
    
                 a. Biopsy tissue (either slides or block) from outside institutions will be reviewed
                 to confirm diagnosis.
    
              2. Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging
                 evidence of multicentric or multifocal disease, no pregnant women, and no comorbid
                 conditions precluding surgery)
    
              3. Clinical T1N0M0 invasive carcinoma or Ductal carcinoma in situ (DCIS) < or equal to
                 2cm
    
              4. 60 years of age or older or 50-59 with a low Oncotype score (0-17) Oncotype is not
                 required for women diagnosed with DCIS.
    
              5. Estrogen receptor positive (ER+), Human epidermal growth factor 2 negative (HER2-)
                 HER-2 status is not required for women diagnosed with DCIS.
    
              6. Women of child-bearing potential must consent to use adequate contraception during the
                 course of the study. Female subjects must agree to use a medically acceptable
                 contraceptives including: (1) surgical sterilization (such as a tubal ligation or
                 hysterectomy), (2) approved hormonal contraceptives (such as birth control pills,
                 patches, implants or injections), (3) barrier methods (such as a condom or diaphragm)
                 used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures
                 such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable
                 methods for routine use.
    
              7. White blood cells (WBC) > 3000, Hemoglobin ( Hgb) > 9, platelets >100000 within 30
                 days of consent
    
              8. Eligible for contrasted magnetic resonance imaging (MRI) on initial evaluation with
                 glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within one
                 month will be considered an acceptable alternative and will not be repeated.
    
              9. Outside breast imaging will be reviewed at Duke to confirm findings are consistent
                 with trial eligibility.
    
            Exclusion Criteria:
    
              1. Neoadjuvant chemotherapy
    
              2. Breast implant in the breast to be treated with SBRT
    
              3. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus,
                 rheumatoid arthritis, scleroderma)
    
              4. Subjects unable to receive study treatment planning secondary to body habitus or
                 inability to lie flat on the stomach at length
    
              5. HER2 positive
    
              6. Positive serum pregnancy test
    
              7. Insufficient breast imaging to judge clinical stage
    
              8. Subjects without placement of a biopsy clip at the diagnostic procedure who are
                 unwilling to undergo clip placement.
    
              9. Subjects in whom treatment planning constraints cannot be met
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:50 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Physician reported rates of good/excellent cosmesis.
    Time Frame:Through study completion estimated to be 3 years
    Safety Issue:
    Description:Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points

    Secondary Outcome Measures

    Measure:Ki-67 will be assessed as a measure of tumor response
    Time Frame:Through study completion estimated to be 3 years
    Safety Issue:
    Description:Ki-67 will be assessed in the pre and post radiotherapy tissue samples
    Measure:Patient reported rates of good/excellent cosmesis
    Time Frame:Through study completion estimated to be 3 years
    Safety Issue:
    Description:Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints
    Measure:The impact of radiation on gene expression
    Time Frame:Through study completion estimated to be 3 years
    Safety Issue:
    Description:Gene expression will be assessed using the Affymetrix Human Transcriptome Array (HTA) arrays designed for formalin fixed paraffin embedded (FFPE) samples on pre and post radiation therapy tissue samples.
    Measure:Local control in the treated breast relative to historic controls
    Time Frame:Through study completion estimated to be 5-10 years
    Safety Issue:
    Description:Annual clinical examination combined with breast imaging
    Measure:Assess the impact of RT on circulating cell free DNA
    Time Frame:Through study completion estimated to be 3 years
    Safety Issue:
    Description:Oxidative stress biomarkers will be measured in serum and urine collected at the same timepoints

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Duke University

    Last Updated

    December 7, 2017