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)

Overview

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.

Interventions

• Radiation MRIdian Radiation Treatment Unit
  partial breast irradiation using 3 x 8.2 Gy to the lumpectomy cavity with a 3mm planning tumor volume (PTV) margin

Primary outcome measures

• Physician Reported Cosmesis: 1-year [Time frame: up to 1-year]

Secondary outcome measures (11)

• Participant Quality of Life: BCTOS Survey [Time frame: up to 5 years]
• Participant Quality of Life: Convenience of Care Scale [Time frame: up to 5 years]
• Participant Quality of Life: MOS SF-36 Survey [Time frame: up to 5 years]
• Physician Reported Cosmesis: 3-year [Time frame: up to 3 years]
• Physician Evaluated Fat Necrosis [Time frame: up to 5 years]
• Acute Radiation Toxicity [Time frame: up to 90 days from completion of radiation therapy]
• Late Radiation Toxicity [Time frame: up to 5 years]
• Ipsilateral Breast Tumor Recurrence (IBTR) [Time frame: up to 5 years]
• Ipsilateral Regional Nodal Recurrence [Time frame: up to 5 years]
• Disease Free Survival (DFS) [Time frame: up to 5 years]
• Overall Survival (OS) [Time frame: 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Wisconsin Carbone Cancer Center — Madison

Identifiers

NCT: NCT03936478 · 2019-0322 · NCI-2019-03111 · UW18099 · SMPH\HUMAN ONCO\HUMAN ONCO · A533300 · Protocol Version 5/24/2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗