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

NCT ID: NCT04040569

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-25
• Study Completion Date: 2027-07-31

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.

Detailed Description

Preoperative stereotactic breast radiation may be beneficial as it offers the ability to target smaller treatment volumes than what has been achievable with adjuvant PBI (Nichols IJROBP 2010), track radiobiological response to radiation at time of surgical pathology, and allow the removal of all irradiated tissue to potentially minimize late effects.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. This would be accomplished on the CyberKnife or GammaPod. The GammaPod is a novel device dedicated to S-PBI utilizing a Cobalt-60 source (Yu Med Phys 2013), which offers a highly reproducible prone setup with a mean of 1.8mm of mismatch reported in 15 patients at the University of Maryland on consecutive scans (Yu JCO 2011). Implications of this research are far reaching, including determination of the maximally tolerated dose for preoperative S-PBI, pathologic complete response rates of early stage breast cancer to a predicted radioablative dose, radiographic markers of treatment response (radiomics), and translational research assessing mechanisms of immune and radiation response.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single-fraction stereotactic partial breast radiotherapy

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.

Group Type: EXPERIMENTAL

Radiomics on MRI

Intervention Type: 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.

Interventions

Radiomics on MRI

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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. 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

2. Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam

3. Age >/= 18 years old and female

4. Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy

5. Tumor must be unifocal

6. The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor

7. 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.

8. Clinically and radiographically node negative on ultrasound of the axilla or MRI

9. Estrogen receptor positive or Progesterone receptor positive and Her2neu negative

10. Ability to understand and the willingness to sign a written informed consent.

11. 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

1. Multi-centric disease

2. Prior RT to the involved breast

3. Tumor size >3cm

4. 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

5. 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

6. Patients unable to have an MRI or contrast enhanced digital mammography (CEDM)

7. Prior ipsilateral breast cancer

8. Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging

9. Patients with active Lupus or scleroderma

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Asal Rahimi

ASSOC PROFESSOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Asal Rahimi, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Countries

United States

Other Identifiers

2019-1183

Identifier Type: -

Identifier Source: org_study_id