A Phase I Dose Escalation Study of Single Fraction Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer

NCT04040569 | Active Not Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 2019-1183
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 (7)

• Cosmesis outcome

  5 years

• Local Control

  5 years

• Acute Toxicity

  90 Days

• Late Toxicity

  24 Months

• Rates of Surgical Morbidity

  5 years

Study Arms (1)

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

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.

Single-fraction stereotactic partial breast radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female only study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• 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.

  PMID: 41236737 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Asal Rahimi, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOC PROFESSOR

Model Details: All patients in each dose cohort will be treated as a single group for dose escalation. The starting dose for the dose escalation portion will be 30 Gy. Subsequent cohorts of patients will receive an additional 4 Gy per treatment. If significant toxicity is encountered at the starting dose, a de-escalation will occur (step -1) to 26.5 Gy. As we are currently concluding an adjuvant single fraction phase I protocol (ClinicalTrials.gov Identifier: NCT02685332) to 30 Gy in a single fraction for early stage breast cancer, if we meet our endpoints of this study, we will start our dose escalation at 34Gy instead of the 30 Gy, as safety of the 30 Gy arm will have already been established.

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 31, 2019
• Study Start: December 25, 2019
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)