Clinical trial NCT03936478: Real-Time MRI-Guided 3-Fraction Accelerated Partial Breast Irradiation in Early Breast Cancer
Official title: A Phase II Study of Real-Time MRI-Guided 3-Fraction Accelerated Partial Breast Irradiation in Early Breast Cancer (MAPBI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
DCIS
LCIS
Keywords: cosmesis
cosmetic
breast-conserving therapy
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2019-05-03
Enrollment: 30
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study will have a lead-in phase consisting of 10 patients, followed for 6-months from the date of completion of radiotherapy for the tenth patient. The second phase of accrual (20 patients) will commence only if three or fewer patients (3/10=30%) have CTCAE v 5.0 grade 3 or higher skin toxicity (radiation dermatitis) or Lövey et al. grade 3 or higher fat necrosis.
Primary purpose: TREATMENT

Brief summary: This trial will investigate a novel 3-fraction radiation regimen for participants undergoing breast-conserving therapy (BCT) for early breast cancer that will: 1) significantly reduce the duration of treatment and can be completed in one-week (5 working days) and 2) MRI-guided radiotherapy (MRIdian) would limit the volume of normal tissue radiated and therefore resultant toxicity. The hypothesis is that 3-fraction radiation therapy can be delivered safely without compromising the therapeutic ratio. Participants can expect to be on study for follow up up to 5 years.


Eligibility criteria: Inclusion Criteria:

For all participants

* Participants should have no contraindications to undergo MRI scan as part of radiotherapy planning and treatment.
* Lumpectomy cavity must be clearly visible on CT and MRI scan at radiotherapy simulation.
* Pregnancy test negative in women of child bearing potential (WOCBP).
* The participant must consent to be in the study and must have signed an approved consent form conforming with institutional guidelines.
* Participants with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior and are deemed by their physician to be at low risk for recurrence. Participants with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.

For participants with Invasive Carcinoma

* Suitable:

  * Age: \>=50 years

    * Margins: Negative by at least 2 mm
    * T Stage: Tis or T1
* Cautionary:

  * Age: 40-49 years

    * Margins: Negative by at least 2 mm
    * T Stage: Tis or T1 OR
  * Age: \>=50 years IF participant has at least 1 of the pathologic factors below and does not have any "unsuitable" factors (below)

    * Pathologic Factors:

      * Size 2.1-3.0 cm (size of the invasive component)
      * T2
      * Close margins (\<2 mm)
      * Limited/focal Lymphovascular Space Invasion (LVSI)
      * ER (-)
      * Clinically unifocal with total size 2.1-3.0 cm (Microscopic multifocality allowed, provided the lesion is clinically unifocal (a single discrete lesion by physical examination and ultrasonography/mammography) and the total lesion size (including foci of multifocality and intervening normal breast parenchyma) falls between 2.1 and 3.0 cm).
      * Invasive lobular histology
      * Extensive Intraductal Component (EIC) \<=3 cm

For participants with DCIS

* Suitable Criteria, DCIS allowed if all of the following are met:

  * Screen-detected
  * Low to intermediate nuclear grade
  * Size \<=2.5 cm
  * Resected with margins negative at \>=3mm OR
* Cautionary Criteria:

  * Pure DCIS \<=3 cm if "suitable" criteria not fully met

Exclusion Criteria (unsuitable criteria) :

* Men are not eligible for this study.
* BRCA1/2 mutation positivity.
* Age \< 40 years (American Society for Radiation Oncology (ASTRO) Unsuitable Criteria).
* Positive resection margins on post operative pathology(ASTRO Unsuitable Criteria).
* Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
* Suspicious micro calcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
* Non-epithelial breast malignancies such as sarcoma or lymphoma.
* Proven multicentric carcinoma (invasive cancer or DCIS) (ASTRO Unsuitable Criteria).
* Pure DCIS \>3 cm in size (ASTRO Unsuitable Criteria).
* Presence of extensive intraductal component \>30mm (ASTRO Unsuitable Criteria).
* Paget's disease of the nipple.
* History of previous invasive breast cancer, DCIS, synchronous bilateral invasive or non-invasive breast cancer. (Participants with a history of LCIS treated by surgery alone are eligible.)
* Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation.
* Concurrent therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, Aromatase Inhibitors or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention or neoadjuvant therapy.
* Breast implants.
* Prior breast or thoracic radiotherapy for any condition or treatment plan that includes regional nodal irradiation.
* Collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma.
* Pregnancy or lactation at the time of treatment. Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the participant from meeting the study requirements.

Primary outcomes:
measure: Physician Reported Cosmesis: 1-year
timeFrame: up to 1-year
Secondary outcomes:
measure: Participant Quality of Life: BCTOS Survey
timeFrame: up to 5 years
measure: Participant Quality of Life: Convenience of Care Scale
timeFrame: up to 5 years
measure: Participant Quality of Life: MOS SF-36 Survey
timeFrame: up to 5 years
measure: Physician Reported Cosmesis: 3-year
timeFrame: up to 3 years
measure: Physician Evaluated Fat Necrosis
timeFrame: up to 5 years
measure: Acute Radiation Toxicity
timeFrame: up to 90 days from completion of radiation therapy
measure: Late Radiation Toxicity
timeFrame: up to 5 years
measure: Ipsilateral Breast Tumor Recurrence (IBTR)
timeFrame: up to 5 years
measure: Ipsilateral Regional Nodal Recurrence
timeFrame: up to 5 years
measure: Disease Free Survival (DFS)
timeFrame: up to 5 years
measure: Overall Survival (OS)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Bethany Anderson, MD
role: PRINCIPAL_INVESTIGATOR
References: