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

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

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.

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.

Inclusion Criteria:

1. Subject must have provided written Informed Consent
2. Subject must have biopsy-proven invasive ductal carcinoma or ductal carcinoma in situ of the breast
3. Subject must be female ≥ 40 years of age
4. Subject's tumor(s) must be < 3.0 cm in greatest diameter by pre-operative assessment
5. Subject's tumor(s) must meet AJCC Tumor Classification: Tis, T1 or T2 (< 3 cm), N0, M0
6. Subject presenting with bilateral breast cancer may be enrolled if BOTH cancers meet all of the inclusion and none of the exclusion criteria
7. Women of child-bearing potential must have a negative pregnancy test within one week of IORT treatment
8. 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:

1. Subject is pregnant or nursing
2. Subject has significant auto-immune disease
3. Subject has a pacemaker present in the field of radiation or quadrant of the breast cancer
4. Subject has biopsy-proven multifocal breast cancer
5. Subject has multi-centric breast cancer
6. Subject has known lympho-vascular invasion
7. Subject has invasive lobular cancer
8. Subject has undergone neo-adjuvant chemotherapy or neo-adjuvant endocrine therapy for current breast cancer
9. Subject has a history of recurrent breast cancer in the ipsilateral breast
10. Subject has had previous radiation exposure of the involved breast
11. 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
12. Subject has contraindications for radiation
13. Subject considered by the Investigator to be high-risk for breast conservation surgery and/or intra-operative radiation therapy
14. 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.