Study of 3-Day Partial Breast Radiation Therapy in Women With Breast Cancer

Breast Cancer Clinical Trial

Official title:

Ultra-Short External Beam-Based Accelerated Partial Breast Irradiation (APBI): A Phase II Toxicity Study Nested With a Non-inferiority Assessment of APBI in New Patient Cohorts

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04084730
• Other study ID #: 19-300
• Status: Recruiting
• Phase: Phase 2
• Start date: August 30, 2019
• Est. completion date: August 30, 2024

Study information

• Verified date: June 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Atif J Khan, MD
• Phone: 848-225-6334
• Email: khana7[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if the dose of radiation therapy that is effective in producing a treatment response, delivered over a shorter treatment period, is a safe approach that causes few or mild side effects in women with newly diagnosed breast cancer or DCIS who have had a lumpectomy procedure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: August 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Female
• Age >/= 45 years
• Unicentric pathological stage I (pT1 or T2 pN0_M0) invasive ductal breast cancer or DCIS measuring <3 cm in longest diameter on pathology and/or mammogram that is histologically confirmed. If T2, the tumor must be less than 3cm in longest diameter. Note: Women = 70 years or older with T1 invasive ductal carcinoma who are estrogen- receptor positive (ER+) with clinically negative axillary nodes, and do not undergo surgical lymph node mapping or dissection (i.e., if tumor deposit is 0.2 mm or less, regardless of whether the deposit is detected by immunohistochemistry or hematoxylin and eosin staining) will also be eligible
• Histologically negative tumor margin or no tumor in a re-excision specimen on final shaved specimen.
• ECOG Performance Status of 0 or 1.
• Clips must be placed in the lumpectomy cavity at the time of final excision in order to aid in the delineation of the tumor cavity at the time of simulation and radiation delivery.
• Negative serum pregnancy test within 14 days prior to study treatment if a woman has child-bearing potential. Subjects of child bearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Written informed consent obtained from subject and ability for subject or comply with the requirements of the study
• Female subjects of childbearing potential should be willing to use 2 methods or birth control or be surgically sterile or abstain from heterosexual activity for the duration of study participation. Should a woman become pregnant while participating on study, she should inform the treating physician immediately.

Inclusion Criteria for intermediate risk substudy:

• Post-NAC cohort patients: clinical T1 or T2 (less than or equal to 5cm in longest diameter on available imaging) and clinical N0 (on exam and imaging) with pathological ypT0, ypTis, or ypT1 (<=2cm) and ypN0 (any regimen of neoadjuvant chemotherapy agents is allowed) OR
• Oncotype RS score of 26 or higher OR
• PAM50 ROR scored as "HIGH" OR
• Presence or LVI (focal, limited or "not otherwise specified") in the lumpectomy specimen OR
• Age 40-49 years (ALL OF THE FOLLOWING MUST BE TRUE : 1) no history of prior benign breast biopsies, 2) no concomitant or prior atypia in either breast, 3) no concomitant or prior LCIS in either breast, 4) no family history of breast cancer in first degree relatives) OR
• Invasive lobular carcinoma OR
• Surgical margins less than 1 mm to invasive or in-situ disease.

Exclusion Criteria:

• Patients with distant metastasis
• Patients who are pregnant or breastfeeding
• Patients with diffuse (>1 quadrant or >5cm) suspicious microcalcifications or patients with known multicentric OR multifocal disease. (microscopic multifocal disease that may be unifocal and/or appear multifocal due to sectioning is allowed after review with PI).
• Prior radiation therapy to the ipsilateral or contralateral breast or thorax.
• Histological evidence of extensive lymphovascular invasion (LVI)
• Histological evidence of extensive intraductal component (EIC), defined as the presence of intraductal carcinoma both within the primary infiltrating ductal tumor (comprising at least 25% of the tumo area) and intraductal carcinoma present clearly beyond the edges of the invasive tumor.
• Patients are not required to undergo BRCA1 and BRCA2 or other genetic mutation tests in order to enroll on the study. Note: in the event a patient is tested and is found to be a mutation carrier, she would be excluded from the study. It would be an extremely rare/unlikely scenario for patients to be discovered BRCA positive after the completion of PBI, as all patients with risk factors for BRCA mutations (positive family history, Ashkenazi Jewish descent, ER-/PR-/her2-neu-negative receptor status) are usually tested prior to radiation. Should such a situation exist, these patients will be given the option of remaining on the breast conservation paradigm or opting for mastectomy (as is done in this rare scenario is standard of care practice). The patient will be replaced on the trial.
• History of cosmetic or reconstructive breast surgery.
• Medical condition such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus, or connective tissue diseases (lupus, systemic sclerosis, or other collagen vascular diseases) that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have "currently active" malignancies if they have completed therapy and are considered by their physicians to be at <5% risk of relapse within 3 years.
• Patients who are already enrolled in or planning to enroll in other adjuvant systemic therapy protocols for both non-invasive or invasive breast cancer
• Expecting to conceive within the projected duration of the trials, starting with screening visit through 180 days after the last dose of trial treatment
• Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. Bisphosponates are permitted without restriction even during protocol treatment. Note: This does not apply to hormonal therapies such as tamoxifen or AIs, which are permitted. This does not apply to anti-Her2 therapies such as trastuzumab or TDM-1, which are also permitted.
• Ongoing therapy with other investigational agents. Patients may not be receiving any other investigational agents.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma
• Carcinoma, Ductal
• Carcinoma, Ductal, Breast
• DCIS
• DCIS Grade 1
• DCIS Grade 2
• Invasive Ductal Breast Carcinoma
• Invasive Ductal Carcinoma, Breast

Intervention

Radiation:
• Accelerated Partial Breast Irradiation
Treatment will consist of APBI delivered using external beam RT techniques to a dose of 24 Gy in 3 fractions of 8.0 Gy delivered on consecutive weekdays

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Baptist Alliance Miami Cancer Institute	Miami	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity with novel APBI schedule as determined by CTCAE version 5	The study is deemed too toxic if the rate of serious toxicity is >/= 10%.	24 months

External Links

•   Memorial Sloan Kettering Cancer Center