Clinical Trials /

Dose Escalation Study of Single Fraction Early Stage Breast Cancer

NCT04040569

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2019-1183
  • NCT ID: NCT04040569

Conditions

  • Breast Cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Single-fraction stereotactic partial breast radiotherapyExperimentalThe primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the 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.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or
                 tubular) histologies of the breast less than 3 cm (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 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 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
    
              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. Patient unable to have an MRI
    
              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
          
    Maximum Eligible Age:99 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Reach the maximum tolerated dose (MTD) or a dose of 38 Gy total
    Time Frame:5 years
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:University of Texas Southwestern Medical Center

    Last Updated