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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ductal Carcinoma in Situ; Invasive Ductal Carcinoma
• Intervention / Treatment: Radiation: Intra-operative Radiation Therapy - IORT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3165
      • Monash Health / Peter MacCallum Cancer Centre
• Portugal
  • Porto, Portugal
    • Hospital CUF Porto
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • University of Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA
    • Oceanside, California, United States, 92056
      • Tri-City Medical Center
    • Pleasant Hill, California, United States, 94523
      • Diablo Valley Oncology Hematology Medical Group
  • Colorado
    • Denver, Colorado, United States, 80220
      • Western Surgical Care, PC
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Florida
    • Celebration, Florida, United States, 34747
      • Florida Hospital Celebration Health
    • Coral Gables, Florida, United States, 33146
      • Doctors Hospital
    • Stuart, Florida, United States, 34994
      • Martin Health System Center for Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Hospital of Indiana
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21218
      • MedStar Oncology Network - Good Samaritan Hospital
    • Baltimore, Maryland, United States, 21237
      • MedStar Oncology Network - Franklin Square
  • New Hampshire
    • Exeter, New Hampshire, United States, 03833
      • Exeter Hospital
  • New York
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Parkridge Medical Center
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt-Ingram Cancer Center
  • Virginia
    • Woodbridge, Virginia, United States, 22191
      • Sentara Northern Virginia Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intra-operative Radiation Therapy - IORT; Intra-operative Radiation Therapy	Radiation: Intra-operative Radiation Therapy - IORT; Single dose of 20 Gy; Other Names: Electronic Brachytherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xoft, Inc.
• Collaborators: Icad, Inc.
• Investigators: Principal Investigator: A.M. Nisar Syed, MD, Long Beach Memorial Medical Center

Publications and helpful links

General Publications

• Ivanov O, Dickler A, Lum BY, Pellicane JV, Francescatti DS. Twelve-month follow-up results of a trial utilizing Axxent electronic brachytherapy to deliver intraoperative radiation therapy for early-stage breast cancer. Ann Surg Oncol. 2011 Feb;18(2):453-8. doi: 10.1245/s10434-010-1283-x. Epub 2010 Aug 25.
• Dickler A, Ivanov O, Francescatti D. Intraoperative radiation therapy in the treatment of early-stage breast cancer utilizing xoft axxent electronic brachytherapy. World J Surg Oncol. 2009 Mar 2;7:24. doi: 10.1186/1477-7819-7-24.

Helpful Links

• National Cancer Institute Factsheet - Radiation Therapy for Cancer

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2012
• Primary Completion (Estimated): July 12, 2023
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 28, 2012
• First Submitted That Met QC Criteria: July 16, 2012
• First Posted (Estimated): July 19, 2012

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Carcinoma in Situ; Carcinoma; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating
• Other Study ID Numbers: CTPR-0009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared.