A Phase I Dose Escalation Study of Single Fraction Pre-op... | NCT04040569

NCT04040569

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single-fraction stereotactic partial breast radiotherapy	Experimental	The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac,Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer.	Radiation: Radiomics on MRI

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Radiomics on MRI	Radiation	Through extracting and analyzing a large number of features from medical imaging, radiomics has shown promising results in treatment outcome prediction for many diseases including breast cancer (45-50). UTSW physics group has developed several new radiomic approaches and radiomic features, such as a multi-objective radiomics model(51) and a new radiomic "Shell" feature(52). As an exploratory end point for this trial, the investigators will explore the application radiomics using pre-treatment MRI, treatment parameters and clinical characteristics as input to predict pathological response of radiation therapy (XRT) based on pathology report of surgical tissues and local recurrence.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Reach the maximum tolerated dose (MTD)	The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac, Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Done by escalating the dose of SBRT toward the tumorcidal dose of 38 Gy in fraction. Doses will be escalated an additional 3.5-4 Gy per treatment. The phase I portion of the study will be completed when either of the following events occur: 1) the MTD for a cohort is reached or 2) when delivery of a pre-determined highest dose of radiation (38 Gy) that has been deemed likely to be efficacious for treatment of early stage breast cancer is attained.Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.	5 years

Secondary Outcomes

Measure	Description	Time Frame
Cosmesis outcome	Photographs of both breasts will be taken and cosmesis form will be graded by the patient and the radiation oncologist at twelve months from the start of therapy and at yearly intervals thereafter and an independent panel established at UTSW Medical Center will evaluate cosmesis at the end of study. Excellent: When compared to the untreated breast, there is minimal or no difference in the sizes, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance Good: There is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only mild change in the shape Fair: There is obvious difference in the size and shape of the treated breast. This change involves ¼ or less of the breast Poor: Marked change in the appearance of the treated breast involving more than ¼ of breast tissue

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis
Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam
Age >/= 18 years old and female
Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy
Tumor must be unifocal
The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor
Patients must undergo an MRI for work up to aid in tumor delineation and to rule out additional foci of disease. If additional foci of disease are present, they need to have a negative biopsy to proceed with treatment.If patient cannot have MRI, contrast enhanced digital mammography (CEDM) is allowed in place of MRI.
Clinically and radiographically node negative on ultrasound of the axilla or MRI
Estrogen receptor positive or Progesterone receptor positive and Her2neu negative
Ability to understand and the willingness to sign a written informed consent.
Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to the start of study and for the duration of radiation therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months

Exclusion Criteria:

Multi-centric disease
Prior RT to the involved breast
Tumor size >3cm
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females
Patients unable to have an MRI or contrast enhanced digital mammography (CEDM)
Prior ipsilateral breast cancer
Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging
Patients with active Lupus or scleroderma

Name	Affiliation	Role
Asal Rahimi, MD	University of Texas Southwestern Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Texas Southwestern Medical Center - Dallas		Dallas	Texas	75390	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41236737	Derived	Rahimi A, Leitch M, Dogan B, Liu Y, Alluri P, Arbab M, Li X, Parsons DDM, Kim DWN, Wandrey N, Farr D, Seiler S, Unni N, Nguyen A, Wooldridge R, Chiu TD, Lu W, Stojadinovic S, Visak J, Nwachukwu C, Patel I, Morgan H, Bahrami S, Stein M, McArthur HL, Sahoo S, Timmerman R. Ablative Preoperative Single-Fraction Radiation Dose Escalation Among Patients With Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2543689. doi: 10.1001/jamanetworkopen.2025.43689.

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases