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Dose Escalation Study of Single Fraction Early Stage Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04040569
Recruitment Status : Recruiting
First Posted : July 31, 2019
Last Update Posted : May 3, 2021
Information provided by (Responsible Party):
Asal Rahimi, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Radiation: Radiomics on MRI Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Single Fraction Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
Actual Study Start Date : December 25, 2019
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : August 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 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.
Radiation: 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.

Primary Outcome Measures :
  1. Reach the maximum tolerated dose (MTD) or a dose of 38 Gy total [ Time Frame: 5 years ]
    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.

  2. Cosmesis outcome [ Time Frame: 5 years ]
    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 for up to 5 years after treatment. In addition, an independent panel established at University of Texas Southwestern Medical Center will evaluate cosmesis at the end of study based on photography.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female only study
Accepts Healthy Volunteers:   No

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 and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04040569

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Contact: Sarah Hardee, MS 2146458525
Contact: Kajal Desai 214-645-8525

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United States, Texas
University of Texas Southwestern Medical Center - Dallas Recruiting
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
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Principal Investigator: Asal Rahimi, MD UT Southwestern Medical Center
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Responsible Party: Asal Rahimi, ASSOC PROFESSOR, University of Texas Southwestern Medical Center Identifier: NCT04040569    
Other Study ID Numbers: 2019-1183
First Posted: July 31, 2019    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases