Safety and Efficacy Study of the Xoft® Axxent® eBx® IORT System®

Study Overview
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Brief Summary
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The purpose of this trial is to assess the safety and efficacy of the Xoft Axxent eBx System when used for single-fraction IORT in early stage breast cancer. Hypothesis: IORT using the Xoft Axxent eBx System is no worse (non-inferior) than whole breast irradiation (WBI) when used as stand-alone radiation treatment in breast conserving therapy in women with early stage breast cancer.

Detailed Description
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The rationale for IORT as the sole radiation therapy is: Favorable preliminary results in feasibility, safety and efficacy outcomes: Accelerated Partial Breast Irradiation (APBI) is an accepted alternative to whole breast irradiation following breast-conserving surgery for early stage breast cancer. Intra-Operative Radiation Therapy (IORT) is a form of APBI that allows radiation to be delivered directly to the open tumor bed following Breast Conservation Surgery (BCS). After 4 years of follow-up, IORT has shown equivalent disease control rates as whole breast irradiation. Direct and timely radiation to the tumor bed: Radiation is delivered at to the target tissue (adjacent to the resection margins at the time of lumpectomy). It avoids treatment delays and eliminates weeks or months of post-surgical radiation therapy during which residual cancer cells might proliferate. An in vitro study showed that un-irradiated wound fluid stimulated the growth of breast cancer cells while irradiated wound fluid did not. Each month of delay in radiation treatment is associated with a 1% increase in the recurrence rate. Huang, et al., found a 5.8% recurrence rate in patients who received WBRT within 8 weeks of BCS compared with a 9.1% recurrence rate in patients who started radiotherapy 9-16 weeks after BCS. Increased patient treatment compliance compared to conventional radiation therapy: Suitable early stage breast cancer patients are able to complete their breast cancer radiotherapy treatment at the time of BCS, which offers a convenient and potentially life-saving benefit to patients who might otherwise omit radiation therapy if it required lengthy travel or time commitments. In addition, healthcare resources, including both personnel and facilities, will be conserved by eliminating the overhead cost of multiple patient visits, eliminating waiting time for patients, and consolidating therapy to one visit combined with the surgical procedure. Available Technology: The Xoft Axxent controller, x-ray source, and balloon applicator are cleared by the United States Food and Drug Administration (FDA) to deliver brachytherapy treatments using high dose rate x-ray radiation. The Xoft Axxent System has been used to treat breast cancer subjects using a multi-fraction APBI technique on an outpatient basis as part of two multi-center studies. The Xoft Axxent System enables the Radiation Oncologist to administer electronic brachytherapy without the use of a radioactive isotope in minimally shielded rooms. Characteristics of the Xoft System that make it well-suited for IORT include its portability and low energy photons, allowing for minimal shielding during the radiation therapy. This protocol has been developed to further study the use of the Xoft Axxent eBx System in the delivery of IORT for subjects with early-stage breast cancer. The Xoft Axxent eBx System will be used according to the United States Food and Drug Administration (FDA) 510(k) cleared labeling; therefore, the use of the technology in this study is considered on-label and within the scope of the FDA cleared indication.

Official Title
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A Safety and Efficacy Study of Intra-Operative Radiation Therapy (IORT) Using the Xoft® Axxent® eBx® System® at the Time of Breast Conservation Surgery for Early Stage Breast Cancer

Conditions
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Invasive Ductal Carcinoma, Ductal Carcinoma in Situ

Intervention / Treatment
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* Radiation: Intra-operative Radiation Therapy - IORT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have provided written Informed Consent Subject must have biopsy-proven invasive ductal carcinoma or ductal carcinoma in situ of the breast Subject must be female ≥ 40 years of age Subject's tumor(s) must be < 3.0 cm in greatest diameter by pre-operative assessment Subject's tumor(s) must meet AJCC Tumor Classification: Tis, T1 or T2 (< 3 cm), N0, M0 Subject presenting with bilateral breast cancer may be enrolled if BOTH cancers meet all of the inclusion and none of the exclusion criteria Women of child-bearing potential must have a negative pregnancy test within one week of IORT treatment Women of child-bearing potential must agree to use adequate contraceptive precautions (defined as oral contraceptives, intrauterine devices, surgical contraceptives or a combination of condom and spermicide) from the time of negative pregnancy test through completion of the radiation treatment period Exclusion Criteria: Subject is pregnant or nursing Subject has significant auto-immune disease Subject has a pacemaker present in the field of radiation or quadrant of the breast cancer Subject has biopsy-proven multifocal breast cancer Subject has multi-centric breast cancer Subject has known lympho-vascular invasion Subject has invasive lobular cancer Subject has undergone neo-adjuvant chemotherapy or neo-adjuvant endocrine therapy for current breast cancer Subject has a history of recurrent breast cancer in the ipsilateral breast Subject has had previous radiation exposure of the involved breast Subject has BRCA 1 or 2 mutations. Note: Testing will only be required for Subjects presenting with bilateral breast cancer; testing is not required for unilateral cancers Subject has contraindications for radiation Subject considered by the Investigator to be high-risk for breast conservation surgery and/or intra-operative radiation therapy Subject has participated in any other clinical investigation that is likely to confound study results or affect study outcome either at the time of IORT or for 3 months prior to IORT.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single 20Gy dose of electronic brachytherapy (IORT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-operative Radiation Therapy - IORT<br>Intra-operative Radiation Therapy | Radiation: Intra-operative Radiation Therapy - IORT<br>* Single dose of 20 Gy<br>* Other names: Electronic Brachytherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the rate of ipsilateral breast tumor recurrence (IBTR) at 5 years | IBTR is defined as biopsy-proven reappearance of cancer in the treated breast. IBTR will be assessed at Month 6, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. A non-inferiority comparison to whole breast irradiation will be made at 5 years. | Change from baseline reported at 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the rate of regional breast tumor recurrence (RBTR) | Regional breast tumor recurrence is defined as biopsy-proven reappearance of cancer in the axilla. Regional recurrence will be assessed at Month 6, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. Regional recurrence rates will be compared to the historical control of WBI at 5 and 10 years. | Report at 10 yrs | 
| Disease Free Survival Rate (DFSR) and Overall Survival rate | Disease free survival (DFS) is defined as the length of time from IORT to any first recurrence. The incidence of disease free survival will be assessed at Month 1, Month 6, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. DFS will be compared to the historical control at 5 and 10 years. | Report at 5 and 10 years | 
| Cosmetic Outcome | Cosmetic outcome will be recorded at baseline, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. a. Physician evaluation will be done using the Harvard Scale. | Report at 5 and 10 yrs | 
| Quality of Life (QOL) | Quality of Life will be assessed at baseline and at each follow-up visit: Month 1, Month 6, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. QOL will be measured using the FACT-B self-reporting questionnaires. | Reported at 5 and 10 yrs | 
| Assess the safety of single fraction IORT at the time of breast conserving surgery for early stage breast cancer | The rates and severity of Adverse Events (AEs), Adverse Device Effects (ADEs), and Unanticipated Adverse Device Effects (UADEs) during and following IORT will be assessed at each follow-up visit. Safety events will be compared to the historical control of WBI at 5 and 10 years. Each event will be classified according to the following: Device Related, Procedure Related or Radiation Related. | On-going monitoring, report at 5 and 10 years | 
| Assess the rate of ipsilateral breast tumor recurrence (IBTR) at 10 years | IBTR is defined as biopsy-proven reappearance of cancer in the treated breast. IBTR will be assessed at Month 6, Month 12, Month 18, Year 2, and then annually through ten (10) year follow-up. A non-inferiority comparison to whole breast irradiation will be made at 10 years. | Change from baseline reported at 10 years |