Clinical trial NCT03581136: Phase II Multi-center Trial Evaluating 5 Fraction Stereotactic Partial Breast Irradiation Using Gammapod
Official title: Phase II Multi-center Trial Evaluating 5 Fraction S-PBI (Stereotactic Partial Breast Irradiation) for Early Stage Breast Cancer Using the GammaPod
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2018-07-10
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Stereotactic radiation has been implemented more than 3 decades ago, initially to radiate benign and later malignant tumors within the brain. Doses up to 24 Gy in one session have been used. Hundreds of thousands of patients have been treated worldwide with very good outcomes . Over the last decade, the stereotactic radiation techniques have been implemented to treat extra-cranial tumors. The challenges of extra cranial tumors were in part target motion during the radiation session, but also accurate re positioning of the patient and of the target volume at time of radiation treatment. Specific immobilization devices are now available to improve accuracy of target localization. Stereotactic radiation therapy is widely available, non-invasive for the patient and less operator dependent as the planning process (from target volume to dose calculation) can be done and verified by different operators through a quality assessment procedure. Stereotactic radiation is a complex type of 3D CRT that is a very attractive technique making the 3D CRT more conformal and more accurate delivery of the prescription dose within the target volume with a very good sparing of surrounding normal tissue. The principles of stereotactic radiation are the following: precise image definition of target volume and OARs, very conformal radiation treatment.

Detailed description: The GammaPod is a new external beam radiotherapy device dedicated for stereotactic radiotherapy of breast cancer (Xcision Medical Systems, LLC, Columbia, Maryland). The design goal of the GammaPod has been the ability to deliver ablative doses with sharp gradients under stereotactic image guidance. Highly focused radiation is achieved at the isocenter due to the cross-firing from 36 radiation arcs generated by rotating 36 individual Cobalt-60 beams.In order to immobilize the breast during imaging and treatment and in order to get a stereotactic localization of the breast target volume, a vacuum-assisted breast immobilization cup with built-in stereotactic frame is used. The patient can be imaged on a CT or MRI wearing the vacuum-assisted breast cup and then be transferred to the GammaPod for treatment. Then, the planner is required to delineate the gross tumor volume (GTV) and its subclinical extensions. Multiple targets within a breast are allowed.Different doses can be prescribed to different targets.One benefit of using the GammaPod over the cyberknife for breast SBRT, is elimination of the need for internal gold fiducial markers, which are required for the cyberknife treatment.

Using a stereotactic technique for APBI allows smaller margins in comparison to a 3DCRT technique. The total expansions on the RAPID trial (3DCRT APBI) were 1.0 cm CTV expansion on the lumpectomy cavity and an additional 1.0 cm for PTV, for a total expansion of 2.0 cm. As a 3DCRT technique was used on the RAPID trial limited number of radiation beams were employed, no Intensity Modulated Radiation Techniques allowed, and the margins used to create a PTV were relatively large (total margin 2 cm).

As the GammaPod will allow us to minimize the volume of normal breast being irradiated, and decrease the PTV volume we hypothesize that a stereotactic technique with the GammaPod will allow us to improve on the 3 year global cosmesis rates (physician and patient) reported in the RAPID trial (3DCRT) by 40% despite 5 daily fractions of SBRT (in contrast to 38.5Gy/10 fractions 3DCRT BID on the RAPID trial) The GammaPod was FDA approved 12-2017.

Eligibility criteria: Inclusion Criteria:

Women who satisfy all of the following conditions will be eligible for this study.

1 DCIS or invasive ductal, medullary, papillary, mucinous (colloid), lobular,or tubular histologies.

2. Age ≥ 18 years. 3. ECOG Performance status 0-2. 4. Women of child-bearing potential must agree to use adequate contraception (barrier method of birth control- condom or diaphragm and spermicidal foam; intrauterine device, prescription birth control pills, or abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

4.1. 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).

  5. Appropriate staging studies identifying as AJCC stage Tis, or T1-T2, N0 (N0i+). The tumor size must be 3 cm or less.

  6. Surgical treatment of the breast with lumpectomy with histologically confirmed margins free of tumor (no ink on margin) for invasive disease, and at least 2mm for Ductal Carcinoma In Situ.. (Re-excision of margins is permitted).

  7. Gross disease within the breast must be unifocal. (Patients with microscopic multifocality are eligible as long as the total extent of tumor, gross and microscopic, occupies a volume with greatest dimension extent of 3 cm or less (regarding the largest diameter of volume occupying space).

  8. Patients with invasive disease are required to have axillary staging including: sentinel node biopsy or axillary dissection. If patients are over age 65, axillary staging is at the discretion of the physician. Patients with DCIS are not required to have axillary staging.

  9. Lymphovascular invasion is allowed if limited or focal.

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

Exclusion Criteria:

1. Men are not eligible for this study.
2. T2(\>3.0 cm), T3, N1, stage III, or stage IV breast cancer
3. Evidence by physical examination or mammography of other suspicious masses, densities, or microcalcifications in either breast, unless biopsied and found to be benign.
4. Patients with non-epithelial breast malignancies such as sarcoma or lymphoma are excluded.
5. Paget's disease of the nipple.
6. Previous thoracic or breast radiation on ipsilateral side. Contralateral breast radiation is not excluded.
7. Treatment plan that includes ipsilateral whole breast or ipsilateral regional nodal irradiation.
8. Any prior treatment with radiation, or chemotherapy (in the neoadjuvant setting) for currently diagnosed breast cancer prior to GammaPod treatment- adjuvant chemotherapy is acceptable.
9. Patients with active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or active skin rash, systemic lupus erythematosis, or scleroderma, or no other exclusions.
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppressed patients or psychiatric illness/social situations that would limit compliance with study requirements.
11. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
12. If the lumpectomy cavity is completely outside of the vacuum assisted breast cup, then patient should not be treated on the GammaPod secondary to concerns of reproducibility.
13. Transplant patients or any patients on immunosuppressive therapy.
14. Breast size that is too large for the breast cup immobilization device.

Primary outcomes:
measure: Patient Cosmesis
timeFrame: 3 Years
Secondary outcomes:
measure: Ipsilateral Breast Recurrence Rate
timeFrame: 3 Years
measure: Disease Specific Survival
timeFrame: 3 Years
measure: Distant Disease-Free Interval
timeFrame: 3 Years
measure: Recurrence Free Survival
timeFrame: 3 Years
measure: Treatment Related Toxicity
timeFrame: 18 Months
measure: Evaluation of Cosmesis from Serial Photography
timeFrame: 3 Years
measure: Evaluation of Patient Cosmesis
timeFrame: 3 Years
measure: Physician Cosmesis
timeFrame: 3 Years
Other outcomes:
measure: Health-Related Quality of Life Using EQ-5D
timeFrame: 5 years
measure: Quality of Life Using BREAST-Q
timeFrame: 5 Years
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Dallas
country: United States
facility: UT Southwestern Medical Centre
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Asal Rahimi, MD
role: PRINCIPAL_INVESTIGATOR
References: