Clinical trial NCT04040569: A Phase I Dose Escalation Study of Single Fraction Pre-operative Partial Breast (S-PBI) for 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-07-31
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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. 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Reach the maximum tolerated dose (MTD)
timeFrame: 5 years
Secondary outcomes:
measure: Cosmesis outcome
timeFrame: 5 years
measure: Local Control
timeFrame: 5 years
measure: Acute Toxicity
timeFrame: 90 Days
measure: Late Toxicity
timeFrame: 24 Months
measure: Rates of Surgical Morbidity
timeFrame: 5 years
measure: Pathologic Complete Response Rates
timeFrame: 5 years
measure: Distant Disease-Free Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Dallas
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Asal Rahimi, MD
role: PRINCIPAL_INVESTIGATOR
References: