Clinical Trials /

MRI-Based Preoperative Accelerated Partial Breast Irradiation

NCT02728076

Description:

This study examines the feasibility to deliver accelerated partial breast irradiaiton (APBI) before a lumpectomy is performed. By administering the APBI before the lumpectomy, a smaller volume of breast tissue may be exposed to radiation. The APBI method used in this study is 3D (three dimensional) conformal external beam irradiation. 3D-conformal external beam irradiation uses an X-ray beam to deliver the radiation dose. Traditionally, CT imaging is used to plan treatment. In this study, an MRI will be used. Approximately five to eight weeks after completion of the APBI, the cancer will be surgically removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MRI-Based Preoperative Accelerated Partial Breast Irradiation
  • Official Title: Phase II Study of MRI-Based Preoperative Accelerated Partial Breast Irradiation

Clinical Trial IDs

  • ORG STUDY ID: PRO26847
  • NCT ID: NCT02728076

Conditions

  • Breast Cancer

Purpose

This study examines the feasibility to deliver accelerated partial breast irradiaiton (APBI) before a lumpectomy is performed. By administering the APBI before the lumpectomy, a smaller volume of breast tissue may be exposed to radiation. The APBI method used in this study is 3D (three dimensional) conformal external beam irradiation. 3D-conformal external beam irradiation uses an X-ray beam to deliver the radiation dose. Traditionally, CT imaging is used to plan treatment. In this study, an MRI will be used. Approximately five to eight weeks after completion of the APBI, the cancer will be surgically removed.

Detailed Description

      This study will examine the feasibility, complication rates, cosmetic results and local
      control rate of 3D-CRT confined to the region of the lumpectomy cavity for patients with
      Stage I and IIa (less than or equal to 3 cm) carcinoma of the breast (non-lobular histology)
      treated with APBI using 3D-CRT before lumpectomy. This study also will test the feasibility
      of MRI-based treatment planning for preoperative accelerated partial breast irradiation and
      compare dosimetric data from treatment planning with patients treated on a previous
      institutional post-op APBI protocol. It will also look at overall survival rates. Correlative
      studies include measuring the changes in tumor gene expression and immune response to
      radiation therapy and correlate this with pathologic response.
    

Trial Arms

NameTypeDescriptionInterventions
Radiation Therapy followed by LumpectomExperimentalPhase II-Preoperative MRI-BasedRadiation followed by Lumpectomy

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Pathologically proven diagnosis of invasive breast cancer, clinically stage I-II.
    
              -  Female
    
              -  Age ≥50 years
    
              -  Estrogen receptor positive
    
              -  Patients with both her2 positive and her2 negative tumors are eligible
    
              -  Unifocal disease
    
              -  Invasive ductal carcinoma diagnosed by core needle biopsy
    
              -  Clinically node negative both by physical exam and by ultrasound. All enlarged or
                 abnormal appearing lymph nodes must be biopsied.
    
              -  Zubrod performance status 0-2
    
              -  Study entry must be within 120 days from initial diagnosis of breast cancer.
    
              -  CBC/differential obtained within 14 days prior to study entry, with adequate bone
                 marrow function defined as follows: Absolute neutrophil count ≥ 1,800 cells/mm3;
                 Platelets ≥ 75,000 cells/mm3; Hemoglobin ≥8.0g/dl.
    
              -  Not pregnant or lactating; willing to use acceptable forms of contraception during
                 radiation therapy.
    
              -  Prior breast augmentation, including breast implants, is allowed.
    
              -  Patients with a prior history of contralateral breast cancer will be considered
                 eligible if they completed all treatment (including anti-endocrine therapy) more than
                 five years prior to registration.
    
              -  Patients must not have a prior treatment of malignancy diagnosed or treated within the
                 past five years, with the exception of non-melanomatous skin cancer, carcinoma in situ
                 of the cervix and contralateral breast cancer.
    
              -  Interested patients must meet with a medical oncologist prior to study entry to
                 determine if Oncotype testing is recommended. If recommended and patient is amenable
                 to the possibility of receiving chemotherapy, there must be adequate biopsy tissue for
                 testing. If adequate tissue is not available for the Oncotype testing, patients who
                 are very interested in participation may undergo additional biopsies. If a patient
                 plans to refuse chemotherapy regardless of a high Oncotype results and elects to forgo
                 the test, they will still be eligible for enrollment.
    
              -  Patients must have had estrogen and progesterone receptor analysis performed on the
                 biopsy specimen prior to study entry according to current ASCO/CAP Guideline
                 Recommendations for hormone receptor testing. Testing for her2 neu expression must
                 also be performed and recorded prior to study entry.
    
              -  Appropriate stage and pre-treatment evaluation for protocol entry, including no
                 clinical evidence for distant metastases, based upon the following minimum diagnostic
                 workup:
    
                   -  History/Physical examination, including breast exam (inspection and palpation of
                      the breasts) with documentation of weight and Zubrod Performance Status of 0-2
                      within 28 days prior to study entry.
    
                   -  Right and left mammography within 60 days of diagnostic biopsy establishing
                      diagnosis.
    
                   -  Evaluation of the axilla by ultrasound and biopsy of all enlarged or abnormal
                      appearing lymph nodes within 28 days prior to study entry.
    
                   -  Clip placed within the biopsy proven breast cancer, with verification of
                      placement by mammogram.
    
            Exclusion Criteria:
    
              -  AJCC clinical T3, N1-3, M1, stage IIB, stage III or stage IV breast cancer
    
              -  Prior invasive non-breast malignancy (exceptions include non-melanomatous skin cancer,
                 carcinoma in situ of the cervix, or prior contralateral breast cancer as described in
                 3.1.11) unless disease free and off treatment for a minimum of five years prior to
                 study entry.
    
              -  Multifocal breast cancer
    
              -  Modified Bloom-Richardson Grade 3 disease
    
              -  Estrogen receptor negative disease
    
              -  Lymphovascular space invasion noted on biopsy
    
              -  Invasive lobular carcinoma
    
              -  Purely non-invasive breast cancer (i.e. ductal carcinoma in situ, lobular carcinoma in
                 situ)
    
              -  Non-epithelial breast malignancies such as sarcoma or lymphoma
    
              -  Paget's disease of the nipple
    
              -  Male breast cancer
    
              -  Prior history of radiation therapy to the chest in the region of the ipsilateral
                 breast that would result in overlap of radiation fields.
    
              -  Patients having received or having planned neoadjuvant chemotherapy or concurrent
                 chemotherapy. A recommendation for adjuvant chemotherapy will not preclude
                 eligibility. However, if a patient has an Oncotype score that would lead to a
                 recommendation for systemic chemotherapy (see section 3.1.13), and chemotherapy is
                 planned to be given in the neoadjuvant setting, the patient would then be ineligible
                 for enrollment.
    
              -  Patients who are unable to undergo MRI. This could include patients with a severe
                 allergy to gadolinium contrast or patients with renal function insufficient to receive
                 contrast (GFR less than 30). Patients who have a minor allergy (for example, skin rash
                 or hives) to gadolinium contrast may still be considered for enrollment. These
                 patients would have to receive prophylactic prednisone and diphenhydramine per MCW
                 department of radiology protocol. Such cases should be reviewed with the principal
                 investigator and radiology co-chair prior to enrollment.
    
              -  History of connective tissue disorder, including lupus, dermatomyositis and
                 scleroderma.
    
              -  Zubrod performance status of 3 or greater
    
              -  Known BRCA mutation
    
              -  Medical, psychiatric or other condition that would prevent the patient from receiving
                 the protocol therapy or providing informed consent.
    
              -  Patients, who under the best estimates of the treating radiation oncologist, have a
                 life expectancy of 10 years or less.
    
              -  Patients who are pregnant.
    
              -  Severe, active co-morbidity, defined as follows:
    
                   -  Unstable angina and/or congestive heart failure requiring hospitalization within
                      the last 6 months;
    
                   -  Transmural myocardial infarction within the last 6 months;
    
                   -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                      of registration;
    
                   -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                      requiring hospitalization or precluding study therapy within 30 days before
                      registration;
    
                   -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                      note, however, that laboratory tests for liver function and coagulation
                      parameters are not required for entry into this protocol
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:50 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Postoperative Complication Rates following Preoperative APBI
    Time Frame:4 Months
    Safety Issue:
    Description:Postoperative complications (the primary endpoint of the study) will be defined as any complication occurring within three months of surgery. These will be measured by CTCAE. The complication rate measured on this study will be compared to a historical control of 32% of patients. This will be measured on an individual patient level. A surgical complication rate that exceeds 31% will be considered unacceptable and result in a negative study. A postoperative complication rate of 14% or less will be considered a successful demonstration of the safety of this treatment.

    Secondary Outcome Measures

    Measure:Cosmetic Outcomes
    Time Frame:5 Years
    Safety Issue:
    Description:Cosmesis will be judged by the patient, radiation oncologist and/or surgeon, at stated follow-up intervals. Cosmetic assessments will be assessed using a 4-point scale.
    Measure:Measure Rates of Fibrosis and Pain
    Time Frame:5 Years
    Safety Issue:
    Description:Patient reported average and worst pain in the treated breast. Radiation Therapy Oncology Group (RTOG) Late Radiation Morbidity Scoring Scheme, rate of Grade 2+ subcutaneous fibrosis. (Statistics: Kaplan-Meier survival estimates or estimate of the cumulative incidence rate will be used where censoring or competing risks occur (local control, cosmetic outcomes, fibrosis, and pain).)
    Measure:Rates of Re-excision
    Time Frame:5 Years
    Safety Issue:
    Description:The need for surgical re-excision after the initial lumpectomy because of close or positive margins will be determined by the treating surgeon and radiation oncologist. For any patient with a positive margin, re-excision is required unless technically not possible (i.e. poor anesthesia risk for the patient, inability to resect additional breast tissue at the site of the positive margin). The re-excision rate and rate of partial/complete response with be estimated with exact confidence intervals, and compared to historical controls using Chi-Square or Fisher's exact tests.
    Measure:Overall Survival
    Time Frame:5 Years
    Safety Issue:
    Description:A final analysis will occur when all patients have been followed up for five years. Record long term outcomes of local recurrence rates and overall survival of patients treated with this modality.
    Measure:Feasibility of MRI-based Treatment Planning
    Time Frame:5 Years
    Safety Issue:
    Description:Demonstrate the feasibility of MRI-based treatment planning for preoperative APBI and compare dosimetric data from treatment planning with patients treated on a previous institutional post-op APBI protocol.
    Measure:Local Control
    Time Frame:5 Years
    Safety Issue:
    Description:Local tumor control defined as reappearance of the tumor in the ipsilateral breast.
    Measure:Radiologic and Pathologic Response
    Time Frame:5 Years
    Safety Issue:
    Description:Tumor response will be assessed using the RECIST and mRECIST criteria.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Medical College of Wisconsin

    Trial Keywords

    • Breast Cancer
    • Accelerated Partial Breast Irradiation

    Last Updated

    June 12, 2017