Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02482376
Recruitment Status : Recruiting
First Posted : June 26, 2015
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE June 22, 2015
First Posted Date  ICMJE June 26, 2015
Last Update Posted Date October 18, 2019
Actual Study Start Date  ICMJE October 21, 2015
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
Physician reported rates of good/excellent cosmesis. [ Time Frame: Through study completion estimated to be 3 years ]
Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2015)
The rate of pathologic complete response to radiation at the time of surgery. [ Time Frame: 8-12 weeks post radiation therapy delivery ]
Six weeks after radiation, subjects will be taken for surgical resection. Subjects without residual invasive or in situ carcinoma will be considered complete responders.
Change History Complete list of historical versions of study NCT02482376 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
  • Ki-67 will be assessed as a measure of tumor response [ Time Frame: Through study completion estimated to be 3 years ]
    Ki-67 will be assessed in the pre and post radiotherapy tissue samples
  • Patient reported rates of good/excellent cosmesis [ Time Frame: Through study completion estimated to be 3 years ]
    Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints
  • The impact of radiation on gene expression [ Time Frame: Through study completion estimated to be 3 years ]
    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.
  • Local control in the treated breast relative to historic controls [ Time Frame: Through study completion estimated to be 5-10 years ]
    Annual clinical examination combined with breast imaging
  • Assess the impact of RT on circulating cell free DNA [ Time Frame: Through study completion estimated to be 3 years ]
    Oxidative stress biomarkers will be measured in serum and urine collected at the same timepoints
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2015)
  • Physician reported rates of good/excellent cosmesis. [ Time Frame: Documented at baseline, 1, 2 and 3 years post treatment ]
    Physician will independently complete the physician Radiation Therapy Oncology Group (RTOG) cosmesis scale at the designated time points
  • Patient reported rates of good/excellent cosmesis [ Time Frame: Documented at baseline, 1,2 and 3 years post treatment ]
    Patients will independently complete the patient Radiation Therapy Oncology Group (RTOG) cosmesis scale at designated timepoints
  • The impact of radiation on gene expression [ Time Frame: 8-12 weeks after radiation therapy delivery ]
    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. b. KI-67 will be assessed in the pre and post radiotherapy tissue samples
  • Local control in the treated breast relative to historic controls [ Time Frame: 5-10 years ]
    Annual clinical examination combined with breast imaging
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer
Official Title  ICMJE A Phase II Preoperative Single-Fraction Partial Breast Radiotherapy in Early Stage Breast Cancer: Analysis of Pathologic Response
Brief Summary

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Radiation: Stereotactic body radiotherapy ( SBRT)
Single fraction of 21 Gy stereotactic radiotherapy (SBRT)delivered pre-operatively to subjects with early stage breast cancer
Other Name: SBRT
Study Arms  ICMJE Single arm 21Gy stereotactic radiotherapy
Subjects will receive a single fraction of 21Gy of stereotactic radiotherapy before proceeding to surgery.
Intervention: Radiation: Stereotactic body radiotherapy ( SBRT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2017)
100
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2015)
40
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eileen Duffy, BNS OCN 919 6683726
Contact: Joan Cahill, BNS OCN CCRP 919 6683726
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02482376
Other Study ID Numbers  ICMJE Pro00063848
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE Gateway for Cancer Research
Investigators  ICMJE
Principal Investigator: Rachel Blitzblau, MD PhD Duke University Health System
PRS Account Duke University
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP