A Pilot Study of Applying New Device Technologies for Tissue Expander/Implant-Based Breast Reconstruction (Blossom Syringe Assist Device)
Phase: NA
Conditions: Breast Carcinoma, Breast Disorder
Sponsor: Stanford University

 
 
 
 
A Pilot Study of Applying New Device Technologies for Tissue 
Expander/Implant-Based Breast Reconstruction (Blossom Syringe Assist 
Device) 
Study Protocol and Statistical Analysis Plan 
NCT03657069 
January 18, 2017 

 
1 
 
 
 
 
TITLE: A Pilot Study of Applying New Device Technologies for Tissue Expander/Implant-
Based Breast Reconstruction (Blossom Syringe Assist Device) 
 
Coordinating Center 
Stanford Cancer Institute 
875 Blake Wilbur Drive 
Stanford, CA 94305 
 
Protocol Director  
Dung H. Nguyen MD PharmD1 
770 Welch Road, Suite 400 
Palo Alto, CA 94304 
(650) 725-2766 
(650) 725-6605 
nguyendh@stanford.edu 
 
Biostatistician 
MB ChB MRCS (Eng)1,2 
@hotmail.com 
 
Co-Investigators 
Danielle H. Rochlin, MD1 
drochlin@stanford.edu 
 
Kristine C. Rustad, MD1 
krustad@stanford.edu 
 
Study Coordinator 
1 
770 Welch Road, 
 
Palo Alto, CA 94304 
(650) 725-2766 
(650) 725-6605 
@stanford.edu 
 
 
1Division of Plastic and Reconstructive Surgery, Stanford University, Palo Alto, CA USA 
2Division of Plastic and Reconstructive Surgery, Royal Free Hospital NHS Trust, London UK 
 
 
Version 2 / Version Date: (01/18/17) 

Protocol Version # 2 
2 
 
  
TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS ............................................................................................................. 4 
SCHEMA ....................................................................................................................................... 5 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS (EXAMPLE) ...................... 6 
1. OBJECTIVES ........................................................................................................................ 7 
1.1. PRIMARY OBJECTIVE ............................................................................................................  
1.2. SECONDARY OBJECTIVES ......................................................................................................  
2. BACKGROUND .................................................................................................................... 7 
2.1 STUDY DISEASE ....................................................................................................................  
2.2 STUDY AGENT/DEVICE/PROCEDURE .....................................................................................  
2.3 RATIONALE ...........................................................................................................................  
2.4 STUDY DESIGN .....................................................................................................................  
2.5 CORRELATIVE STUDIES BACKGROUND .................................................................................  
3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ......................... 8 
3.1 INCLUSION CRITERIA ............................................................................................................  
3.2 EXCLUSION CRITERIA ...........................................................................................................  
3.3 INFORMED CONSENT PROCESS ..............................................................................................  
3.4       RANDOMIZATION PROCEDURES ...........................................................................................  
3.5 STUDY TIMELINE ..................................................................................................................  
4. TREATMENT PLAN ............................................................................................................ 9 
4.1 GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE GUIDELINES ......................  
4.2 CRITERIA FOR REMOVAL FROM STUDY .................................................................................  
4.3 ALTERNATIVES .....................................................................................................................  
5. INVESTIGATIONAL AGENT/DEVICE/PROCEDURE INFORMATION ................ 11 
5.1 
 INVESTIGATIONAL AGENT/DEVICE/PROCEDURE ..................................................................  
5.2 AVAILABILITY ......................................................................................................................  
5.3 AGENT ORDERING ................................................................................................................  
5.4 AGENT ACCOUNTABILITY .....................................................................................................  
6. DOSE MODIFICATIONS .................................................................................................. 12 
7. ADVERSE EVENTS AND REPORTING PROCEDURES ............................................ 12 
7.1 POTENTIAL ADVERSE EVENTS ..............................................................................................  
7.2 ADVERSE EVENT REPORTING................................................................................................  
8. CORRELATIVE/SPECIAL STUDIES ............................................................................. 13 
8.1 LABORATORY CORRELATIVE STUDIES ..................................................................................  
9. STUDY CALENDAR .......................................................................................................... 14 
10. MEASUREMENT.............................................................................................................. 14 
10.1  PRIMARY AND SECONDARY OUTCOME MEASURES ................................................................  
10.2  SECONDARY OUTCOME .........................................................................................................  

Protocol Version # 2 
3 
 
11. REGULATORY CONSIDERATIONS ........................................................................... 16 
11.1 INSTITUTIONAL REVIEW OF PROTOCOL .................................................................................  
11.2 DATA AND SAFETY MONITORING PLAN ................................................................................  
11.3 DATA MANAGEMENT PLAN ..................................................................................................  
12. STATISTICAL CONSIDERATIONS ............................................................................. 16 
12.1 STATISTICAL DESIGN ............................................................................................................  
12.2 INTERIM ANALYSES ...............................................................................................................  
12.3 DESCRIPTIVE STATISTICS AND EXPLORATORY DATA ANALYSIS ..........................................  
12.4 PRIMARY ANALYSIS ..............................................................................................................  
12.5 SECONDARY ANALYSIS .........................................................................................................  
12.6  SAMPLE SIZE .........................................................................................................................  
12.7 CRITERIA FOR FUTURE STUDIES ............................................................................................  
13. REFERENCES ................................................................................................................... 18 
APPENDICES ............................................................................................................................. 20 
APPENDIX A: PARTICIPANT ELIGIBILITY CHECKLIST .................................................................  
 

Protocol Version # 2 
4 
 
PROTOCOL SYNOPSIS  
 
 
TITLE 
Applying New Device Technologies for Tissue 
Expander/Implant-Based Breast Reconstruction 
(Blossom Syringe Assist Device)  
STUDY PHASE 
I 
INDICATION 
To evaluate a device that has the potential to 
achieve the same reconstructive goals as 
conventional tissue expansion in a shorter period 
of time and while avoiding frequent injections 
through the skin, which cause patient discomfort 
and require many clinic visits.  
INVESTIGATIONAL PRODUCT OR 
PROCEDURE 
Blossom Smart Expander Technology (Syringe 
Assist Device) 
PRIMARY OBJECTIVE(S) 
Effectiveness of Blossom Device in 1st stage of 
expander to implant breast reconstruction (time 
to expansion) 
SECONDARY OBJECTIVE(S) 
Patient satisfaction, self-reported pain, incidence 
of complications 
TREATMENT SUMMARY 
Consenting patients will be prospectively 
enrolled. This investigational device slowly and 
continuously injects a small amount of saline 
based on pressure and volume in the expander. 
The expander devices will be inserted beneath 
the pectoralis major muscle in the usual fashion 
immediately after mastectomy. The nature of the 
surgery remains identical to that for 
conventional breast tissue expander insertion. 
Postoperative follow-up with documentation of 
clinical data will occur on a weekly basis until 
completion of breast expansion along with 
stabilization of surgical scars and percutaneous 
drain removal. Monthly follow-up, as indicated, 
will occur in preparation for the second stage 
expander to definitive implant exchange 
surgery. 
SAMPLE SIZE  
10 

Protocol Version # 2
5
SCHEMA
Patients prospectively enrolled for pilot study. Must meet inclusion and exclusion criteria 
(please refer to sections 3.1 and 3.2 for specific criteria) n=10
Surgical insertion of Blossom Syringe Assist Device/Mentor SPECTRUM® adjustable 
saline breast implant for expansion (1st stage of 2-staged implant-based breast 
reconstruction)
Postoperative follow-up
Assessment of primary + secondary outcomes

Protocol Version # 2 
6 
 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
 
AE  
Adverse event 
IBR 
Implant-based breast reconstruction 
IRB 
Institutional Review Board 

Protocol Version # 2 
7 
 
1. 
OBJECTIVES 
 
1.1. 
Primary Objective  
The primary objective of this study is to assess the clinical effectiveness of the application of 
Blossom Smart Expander Technology in 2-staged tissue expander/implant-based breast 
reconstruction. This new study may lead to the development of a new approach to tissue 
expander/implant-based breast reconstruction that is better tolerated by patients and decreases 
the total number of clinic visits. Effectiveness will be measured by total time to expansion, 
which is the primary outcome being investigated. 
 
1.2. 
Secondary Objectives 
 
Secondary objectives being investigated include the following: 
  
- Patient Satisfaction  
 
- Patient self-reported pain 
 
- Incidence of complications 
 
2. 
BACKGROUND 
 
2.1 
Study Disease 
Tissue expander/implant-based breast reconstruction is the most common form of breast 
reconstruction in North America following mastectomy in patients diagnosed with  
either breast cancer or strong genetic predisposition for breast cancer. The conventional breast 
tissue expander requires weekly-biweekly injections of saline through the skin and into the 
integrated port using a needle and syringe in order to expand breast skin (standard of care). This 
is an office procedure and can be uncomfortable for patients, and also results in multiple clinic 
visits and a time delay (usually several weeks to months) until final expansion volume is 
achieved. Once this expansion process is complete, the patient may proceed to the 2nd stage 
surgery where the expander is exchanged for a definitive breast implant, thereby effectively 
completing reconstruction of the breast mound. 
 
In contrast to the standard of care, the current clinical trial will evaluate the Blossom device as a 
method to continuously fill the expander with small quantities of saline based on pressure within 
the chambr and can potentially complete expansion within several weeks without the need for 
frequent office visits.  
 
2.2 
Study Agent/Device/Procedure 
Blossom Smart Expander Technology (Syringe Assist Device), currently commercially 
available, aims to achieve the same reconstructive goals as conventional tissue expansion while 
avoiding frequent injections through the skin. The Blossom Syringe Assist Device is intended to 
be used to assist the clinician in the delivery of sterile saline to fill temporary, removable tissue 
expanders. This device includes a battery powered controller to provide a regulated method for 
delivery of a specific volume of saline at a specific rate. Supplied with the controller in a kit are 
the following components: single use sterile 10cc luer lock piston syringe, transfer set with 
proximal connection to the controller, and saline reservoir including distal connections to the 

Protocol Version # 2 
8 
 
inflation port of the expander. The fluid path is clear, allowing for visual inspection of the 
content.  
 
The Blossom device is a tissue expander accessory that allows for slow and continuous injection 
of small amounts of saline, from an external pouch and based on precise pressure and volume 
measurements, into breast expander implants.  
 
Blossom Syringe Assist Device is FDA 510K approved. It does not require an Investigational 
New Drug application (IND).  
 
2.3 
Rationale 
Weekly or biweekly injections of saline through the skin during conventional tissue expansion 
result in multiple clinic visits, patient discomfort, and a time delay (usually several weeks to 
months) until final expansion volume is achieved. The Blossom device may be employed in 
patients opting for 2-staged implant-based (expander to implant) breast reconstruction, while 
avoiding the aforementioned drawbacks of serial percutaneous saline injections via automated 
slow continuous injection based on pressure and volumetric measurements. 
 
2.4 
Study Design 
• The primary purpose is a protocol designed to evaluate one or more interventions 
for treating a disease, syndrome, or condition.  
• The interventional model is single group  
• There is one intervention arm (Blossom Smart Expander Technology [Syringe 
Assist Device])  
• The study will be open (no masking is used).   
• The study will not be randomized.  
• The primary outcome that the protocol is designed to evaluate is safety/efficacy.  
 
2.5 
Correlative Studies Background 
There are no planned correlative studies. 
 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
 Refer to the Participant Eligibility Checklist in Appendix A.  
 
There will be an assessment of how many people are approached and how many people 
decline or are ineligible, including the reasons for exclusions.  
 
3.1 
Inclusion Criteria 
 
3.1.1 Diagnosis of breast cancer or reason for prophylactic mastectomy (e.g., BRCA mutation 
and/or strong family history of breast cancer), both unilateral or bilateral mastectomy. 
 

Protocol Version # 2 
9 
 
3.1.2 No prior breast surgery (excluding biopsy and lumpectomy) or breast radiation.  
  
3.1.3 Women age 18 years or older, no race-ethnic restrictions. 
 
3.1.4 Ability to understand and the willingness to sign a written informed consent document. 
 
 
3.1.5 No life expectancy restrictions. 
  
 
3.1.6 ECOG or Karnofsky Performance Status will not be employed.  
 
 
3.1.7 No requirements for organ and marrow function. 
 
3.2 
Exclusion Criteria 
 
3.2.1 Recent steroid use. 
 
3.2.2 No major medical comorbidities (defined as ASA III or greater6)  
 
3.2.3 No connective tissue disorder 
 
3.2.4 Prior breast surgery, excluding biopsy and lumpectomy 
 
3.2.5 History of or plan for breast radiation 
 
3.2.6 Pregnancy and nursing patients will be excluded from the study 
 
3.2.7 No restrictions regarding use of other Investigational Agents. 
 
3.2.8 No exclusion criteria related to history of allergic reactions. 
 
3.2.9 No exclusion criteria relating to concomitant medications or substances that have the  
            potential to affect the activity or pharmacokinetics of the study agent, except as per 3.2.1.  
 
3.2.10 No other agent-specific exclusion criteria. 
 
3.2.11 No exclusion of cancer survivors or those who are HIV-positive.   
 
3.3 
Informed Consent Process 
All participants must be provided a consent form describing the study with sufficient information 
for participants to make an informed decision regarding their participation.  Participants must 
sign the IRB approved informed consent prior to participation in any study specific procedure. 
The participant must receive a copy of the signed and dated consent document.  The original 
signed copy of the consent document must be retained in the medical record or research file.  

Protocol Version # 2 
10 
 
 
3.4       Randomization Procedures 
N/A  
 
 
3.5 
Study Timeline 
Primary Completion: 
The study will reach primary completion 12 months from the time the study opens to accrual.  
 
Study Completion: 
The study will reach study completion 24 months from the time the study opens to accrual. 
 
4. 
TREATMENT PLAN 
All consenting patients presenting to Dr. Dung Nguyen's breast reconstruction clinic and  
opting for immediate 2-staged tissue expander/implant-based breast reconstruction after  
mastectomy will be given the option of study enrollment. Consenting patients will be 
prospectively enrolled to undergo 2-staged IBR with the application Blossom Smart Expander 
Technology (Syringe Assist Device) in the first stage (tissue expansion). The Mentor Spectrum 
saline implant (FDA approved device) is placed in the mastectomy skin pocket at the time of 
reconstruction. The fill tube is externalized and connected to the Blossom Syringe Assist Device 
that controls the gradual continuous fill of the Mentor Spectrum based on the pressure within the 
mastectomy skin pocket. The Mentor Spectrum implant stays in the patient for the duration of 
the expansion, approximately 2-3 weeks. The Blossom device is external and is detachable. 
BlossomTM Instructions for Use that a saline bag of no greater than 250cc be connected to the 
transfer set. If required, additional saline bags can be attached. There are 3 rates of infusion that 
can be selected by the physician to achieve optimal results. The volume delievered is determined 
by the difference in the initial and remaining volume in the saline bag. The nature of the surgery 
remains identical to that employed for conventional breast tissue expander insertion following 
mastectomy.  The Blossom device is connected at the time of surgery. The decision to initiate 
filling immediately intraoperative versus in the clinic is determined by the surgeon based on 
conition of the patient’s skin. This decision making process is similarly being done currently 
with conventional tissue expander reconstruction.  This device can be used in immediate or 
delayed reconstruction. The pressue sensing technology and the ability to infuse very small 
quantity of liquid continuously offer a key advantage over conventional TE approach to allow 
patients with immediate TE reconstruction to complete their expansion earlier and safely. 
Postoperative follow-up will occur within 1 week of surgery. Weekly follow-ups with 
documentation of clinical data throughout will also take place until completion of the expansion, 
stabilization of surgical scars, and removal of all percutaneous drains. Thereafter, follow-ups will 
be scheduled as needed (monthly) according to usual clinical practice in implant-based breast 
reconstruction in preparation for the second stage expander to definitive implant exchange. Time 
to expansion completion, patient satisfaction (including self-reported pain), and incidence of 
complications will be recorded throughout the follow-up period. 
 

Protocol Version # 2 
11 
 
A video recording of 1-2 cases in the study group may occur (intraoperative). The purpose of 
these videos would be to demonstrate the placement of the Blossom Smart Expander Technology 
in-situ. These recordings may also supplement eventual publications and scientific presentations. 
Only patients specifically consenting to video recording will be affected. All videos will be 
deidentified (no facial identification possible). Videos will be kept in a secure, encrypted 
location and destroyed within 5 years following completion of the study. Photography will be 
routinely used pre- and postoperatively, with appropriate patient consent, in order to document 
aesthetic outcomes. Tissue samples will not be retained for future research.  
 
4.1 
General Concomitant Medication and Supportive Care Guidelines 
The Women's Cancer Center is a collaborative environment for treatment of women with breast 
disease. Physicians remain apprised of other protocols in which their patients are involved 
through direct communication with other physicians and review of patients' electronic medical 
record. Patients in our study will not be routinely involved in more than one study, though this 
would not preclude study participation. There will be no routine use of concomitant medications 
or any additional supportive care medications or treatments. Concomitant radiotherapy is an 
exclusion criterion for study participation.  
Procedures performed are a normal part of clinical management for this condition. Risks 
associated with the Blossom device include device malfunction. Risks also include those 
common to all tissue expanders used in conventional tissue expansion (standard of care): 
infection, extrusion, and pain. Importantly, in the event of any pain due to volume fill, the 
Blossom technology device can easily be disconnected by the patient in a reliable and safe 
manner.  
The care of the port is much like drain care. The patient will have a demonstration of the 
Blossom Device and how to clean the port by the Nurse Coordinator at the time of pre-op. This 
will be reinforced post-op and in clinic much like conventional tissue expander reconstruction. 
The patient will also receive written patient instructions. 
4.2 
Criteria for Removal from Study 
Patients will be removed from the study in the event of withdrawal of consent. Patients would 
then be eligible for placement of conventional tissue expanders. The study as a whole would only 
be terminated prematurely if the Blossom device proved to be clearly more ineffective, since 
traditional tissue expansion is still a safe and effective method of expansion. The study will 
terminate if there is increased incidence of complications noted above rates of complications 
reported in the standard tissue expander-implant reconstruction. 
 
4.3 
Alternatives 
Patients will be monitored at routine clinic follow-up visits. They are counseled on warning signs 
that should prompt a call to their physician, and provided with a phone number at which they can 
reach a physician for advice at all hours. None of these methods of protection jeopardizes patient 
confidentiality beyond the risks inherent in routine patient care. A study participant selected for 
the Blossom Smart Expander Technology tissue expander/implant-based breast reconstruction 
arm may undergo the alternative, conventional tissue expander/implant-based breast 

Protocol Version # 2 
12 
 
reconstruction, only if she chooses to withdraw from the study. There are no other alternatives 
available within the study.  
 
5. 
INVESTIGATIONAL AGENT/DEVICE/PROCEDURE INFORMATION 
5.1 
 Investigational Agent/Device/Procedure   
Blossom Smart Expander Technology is a FDA-approved (510K) medical device. It consists of a 
syringe assist device connected to the Mentor SPECTRUM® Adjustable Saline Breast Implant. 
Blossom Smart Expander Technology aims to achieve the same aforementioned reconstructive 
goals of traditional breast tissue expander implants while obviating the frequent percutaneous 
injections by means of automated slow and continuous saline injection based on pressure and 
volume measurements in the associated expander implant (Mentor SPECTRUM®). The Mentor 
Spectrum device is a onetime use device that is placed during surgery, but it is designed to allow 
providers to adjust volume (add or take out fluid from the prosthesis) after surgery in an 
outpatient setting through the remote port. In this study the Mentor Spectrum will be used in 
exactly the same way except rather than implant the remote port, the fill tube will be exteriorized 
at for a few centimeters to connect it to the Blossom controller device. The Mentor Spectrum 
will be treated like other tissue expanders in that at the conclusion of the expansion process the 
fill tube will be removed and ultimately the Spectrum will be removed and replaced with a 
permanent implant. The Mentor Spectrum can be used as a permanent implant in patients who 
desire a saline implant after removal of the infusion tube. 
The Blossom Syringe Assist Device is intended to be used to assist the clinician in the delivery 
of sterile saline to fill temporary, removable tissue expanders. This device includes a battery 
powered controller to provide a regulated method for delivery of a specific volume of saline at a 
specific rate. Supplied with the controller in a kit are the following components: single use sterile 
10cc luer lock piston syringe, transfer set with proximal connection to the controller, and saline 
reservoir including distal connections to the inflation port of the expander.  The controller 
(pump) is 6.5” long, 3.5” tall, 1.25” wide and weighs 0.7lbs. AA batteries are changed every 3 
days. There is a low battery indicator to remind patients to change the AA batteries every 3 days. 
The fluid path is clear, allowing for visual inspection of the content. If the device fails and a 
manual process is used. The device can be detached from the fill tube. The fill tube of the Mentor 
Spectrum device is externalized much like a drain and connected to the Blossom Syringe 
Assisted Device. It is expected to have the similar rate of infection as a standard drain. 
 
A Mentor Spectrum® adjustable saline breast implant for expansion, coupled with the Blossom 
Syringe Assist device, will be inserted beneath the pectoralis major muscle in the usual fashion 
immediately after mastectomy. The nature of the surgery remains identical to that employed for 
conventional breast tissue expander insertion following mastectomy . 
 
Please see attached instruction brochure for further information on Blossom Technology. 
 
5.2 
Availability 
Marz Medical 
 

Protocol Version # 2 
13 
 
5.3 
Agent Ordering 
The devices will be requested from Marz Medical directly, as needed.  
 
Marz Medical, Inc. 
2500 Hospital Drive, Bldg 9 
Mountain View, CA 94040 
510-441-4017 
 
5.4 
Agent Accountability 
The Blossom devices/kits will be stored together with the appropriate ordered breast implants for 
each individual patient. 
 
6. 
DOSE MODIFICATIONS 
No treatment modifications are envisioned. 
If the investigational device were to fail to achieve the projected expansion of the breast skin, 
conversion to the traditional breast expander device with manual percutanous saline injections 
would be carried out, as indicated. 
 
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES 
7.1 
Potential Adverse Events 
 
Since the Blossom Syringe device will be connected to and used with the Mentor SPECTRUM® 
Adjustable Saline Breast Implant the Risks include those common to all breast tissue expander 
implants procedures: capsular contracture, infection, extrusion, malposition, and pain. 
Importantly, these risks are due to the breast expander itself and as such are unavoidable in 
patients undergoing conventional 2-staged IBR. Furthermore, in the event of any pain due to 
volume fill, the Blossom technology device can easily be disconnected by the patient in a reliable 
and safe manner.  
 
7.2 
Adverse Event Reporting 
 
Adverse events will be graded according to CTCAE v4.03.  Both Serious and Non-Serious 
Adverse Events will be clearly noted in source documentation and listed on study specific Case 
Report Forms (CRFs).  The Protocol Director (PD) or designee will assess each Adverse Event 
(AE) to determine whether it is unexpected according to the Informed Consent, Protocol 
Document, or Investigator’s Brochure, and related to the investigation. All Serious Adverse 
Events (SAEs) will be tracked until resolution, or until 30 after the last dose of the study 
treatment.  
 
SAEs CTCAE Grade 3 and above, and all subsequent follow-up reports will be reported to the 
Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) using the study 
specific CRF regardless of the event’s relatedness to the investigation. Following review by the 

Protocol Version # 2 
14 
 
DSMC, events meeting the IRB definition of ‘Unanticipated Problem’ will be reported to the 
IRB using eProtocol within 10 working days of DSMC review, or within 5 working days for 
deaths or life-threatening experiences. 
 
8. 
CORRELATIVE/SPECIAL STUDIES  
N/A 
 

Protocol Version # 2 
15 
 
9. 
STUDY CALENDAR 
 
 
   
Pre-
Study 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
 4 
Wk 
5 
Wk 
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Off Study 
 
Blossom Syringe Assist Device, 
postoperative assessmentsa  
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concurrent meds 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluationa 
 
 
  X --------------------------------------------------------------------------------------------X 
 
 
 
B-HCG 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
aDevice postoperative assessment and adverse events (AEs) evaluation will be conducted on a weekly basis for 12 weeks, with assessments in clinic 
every other week and by phone the alternative every other week.  
NOTE: Baseline exams and tests performed as indicated above. Once investigational device is 
inserted surgically, the patient will undergo follow-up as mentioned previously until the second 
stage expander to implant exchange procedure.  
 
 
 
X 

Protocol Version # 2 
16 
 
10. 
MEASUREMENTS 
10.1  Primary outcome measure: time to full expansion 
 
10.1.1 This outcome will be measured on all subjects.  
 
10.1.2 Defined as number of days until desired expansion volume is achieved. This outcome is 
not assessing a safety issue.  
 
10.1.3 Outcome will be measured by calculating the number of days from expander placement to 
achievement of desired expansion volume.  
 
10.1.4 Measurement time points include date of expander placement and date that desired 
expansion volume is reached. Follow-up will be 12 months.  
 
10.1.5 Response is not the primary outcome.  
 
10.2  Secondary outcome meausure: patient satisfaction  
 
10.2.1 This outcome will be measured on all subjects.  
 
10.2.2 Defined as patient satisfaction with expansion process.  
 
10.2.3 Outcome will be measured by non-validated surveys (Breast Q) administered to patients 
in clinic in order to assess satisfaction. Patients will be asked to rank satisfaction on the 
following scale: very satisfied, somewhat satisfied, neutral, somewhat dissatisfied, very 
dissatisfied.  
 
10.2.4 Measurement time points will be at postoperative clinic visits, which will occur at weekly 
and intervals during the expansion process. Total follow-up will be approximately 12 months.  
 
10.2.5 Response is not the primary outcome.  
 
10.3  Secondary outcome measure: incidence of complications  
 
10.3.1 This outcome will be measured on all subjects.  
 
10.3.2 Defined as complications associated with tissue expansion process, including expander 
extrusion, wound breakdown, infection, and/or device malfunction.   
 
10.3.3 Outcome will be measured by assessment of these patients at postoperative clinic visits 
for these complications.  
 
10.3.4 Measurement time points will be at postoperative clinic visits, which will occur at weekly 
intervals during the expansion process. Follow-up will be approximately 12 months.  

Protocol Version # 2 
17 
 
 
10.3.5 Response is not the primary outcome.  
 
10.4  Secondary outcome meausure: pain with expansion  
 
10.4.1 This outcome will be measured on all subjects.  
 
10.4.2 Defined as self-reported pain associated with expansion process.   
 
10.4.3 Outcome will be measured by non-validated surveys (Breast Q) administered to patients 
in clinic in order to assess pain. Patients will be asked to rank pain level on a scale of 0 to 10, 
with 0 being the least and 10 being the most.  
 
10.4.4 Measurement time points will be at postoperative clinic visits, which will occur at weekly 
intervals during the expansion process. Follow-up will be approximately 12 months.  
 
10.4.5 Response is not the primary outcome.  
 
11. 
REGULATORY CONSIDERATIONS 
11.1 
Institutional Review of Protocol 
The protocol, the proposed informed consent and all forms of participant information related to 
the study (e.g. advertisements used to recruit participants) will be reviewed and approved by the 
Stanford IRB and Stanford Cancer Institute Scientific Review Committee (SRC).  Any changes 
made to the protocol will be submitted as a modification and will be approved by the IRB prior 
to implementation.  The Protocol Director will disseminate the protocol amendment information 
to all participating investigators. 
 
11.2 
Data and Safety Monitoring Plan 
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the 
monitoring entity for this study. The DSMC will audit study-related activities to determine 
whether the study has been conducted in accordance with the protocol, local standard operating 
procedures, FDA regulations, and Good Clinical Practice (GCP).  This may include review of the 
following types of documents participating in the study: regulatory binders, case report forms, 
eligibility checklists, and source documents.  In addition, the DSMC will regularly review 
serious adverse events and protocol deviations associated with the research to ensure the 
protection of human subjects.  Results of the DSMC audit will be communicated to the IRB and 
the appropriate regulatory authorities at the time of continuing review, or in an expedited 
fashion, as needed. 
 
11.3 
Data Management Plan 
The Protocol Director, or his/her designee, will prepare and maintain adequate and accurate 
participant case histories with observations and data pertinent to the study. Study specific Case 
Report Forms (CRFs) will document treatment outcomes for data analysis. Case report forms 

Protocol Version # 2 
18 
 
will be developed using the REDCap database system and will be maintained by Stanford Box 
account. CRFs will be kept in a locked office, only accessible to the research team.  
 
12. 
STATISTICAL CONSIDERATIONS 
12.1 
Statistical Design 
This study is a prospective clinical trial. 
 
12.1.1 Randomization 
N/A 
 
 12.2 Interim analyses 
There are no planned interim analyses 
 
12.3 
Descriptive Statistics and Exploratory Data Analysis 
Measures of central tendency and measures of spread will be performed for the primary outcome 
(time to full expansion, in days) 
 
12.4 
Primary Analysis  
(10.1): Time to full expansion 
 
12.4.1 Analysis Population 
All participants will be included in this analysis. Primary analysis will be an intent-to-treat 
principle. 
 
12.4.2. Analysis Plan 
 
Student’s t-test will be applied to compare the primary outcome to values commonly reported in 
the literature in conventional 2-staged IBR. 
 
12.5 
Secondary Analysis 
 
(10.2): patient satisfaction 
 
(10.3): incidence of complications 
 
(10.4): pain with expansion 
 
 
12.5.1 Analysis Population 
All participants will be included in these secondary analyses. Any missing data will be reported as 

Protocol Version # 2 
19 
 
such in the results.  
 
12.5.2  Analysis Plan 
Survey data for secondary outcomes 10.2 and 10.4, as described in previous sections, will be 
tabulated. Secondary outcome 10.3 will be analyzed with Student’s t-test in order to compare 
with complication rates reported in the literature for conventional 2-staged IBR. 
 
12.6  Sample Size 
12.6.1 Accrual estimates  
 
Ten patients will be recruited prospectively. This is a pilot study. Ample time has been allotted 
for patient recruitment, and ten is a very feasible number so no shortage is expected. In the 
unlikely event that there is difficulty in recruiting a sufficient number of patients at Stanford 
Hospital, additional recruitment efforts at affiliated Stanford sites will be considered, if 
approved. 
 
 
12.6.2 Sample size justification 
 
This is a pilot study. This initial pilot group may provide the basis for proceeding to a 
prospective randomized-controlled trial thereafter.  
 
12.6.3 Effect size justification 
 
The most extensive study on rapid breast expansion post-mastectomy with expander implants 
emanates from Memorial Sloan-Kettering Cancer Center and includes 370 breast reconstructions 
in 314 patients. Mean time until last in-office expansion was reported as 6.6 weeks 
postoperatively3. Among the most highly-cited papers on conventional 2-staged implant-based 
breast reconstruction complications also comes from Memorial Sloan-Kettering Cancer Center 
and incorporates data on 1522 breast reconstructions in 1221 patients. This paper describes an 
overall complication rate of 5.6% for the stage 1 breast tissue expander insertion procedure and 
expansion process in nonradiated patients, which is identical to our study population 
characteristics. Confidence intervals not applicable to these 2 studies. These studies provide the 
ideal baseline to compare to as they include the same target population from a well-respected 
cancer center and high number of patients. 
 
12.7 
Criteria for future studies 
 
As a pilot study, the criteria for success that would justify a fully powered study include: time to 
expansion (primary outcome) faster than described for the conventional technique in the 
literature (p<.05) as well as an incidence of complications comparable to that reported for 
conventional techniques in the literature. Lastly, acceptability by patients (based on the 
aforementioned surveys) will be taken into account. 
 
  

Protocol Version # 2 
20 
 
13. 
REFERENCES 
1 Albornoz CR, Bach PB, Mehrara BJ et al. A paradigm shift in U.S. Breast reconstruction: 
increasing implant rates. Plast Reconstr Surg. 2013;131(1):15-23.  
 
2 Collins N, Sharpe DT. Breast reconstruction by tissue expansion. A retrospective technical 
review of 197 two-stage delayed reconstructions following mastectomy for malignant breast 
disease in 189 patients. Br J Plast Surg. 2000;53(1):37-41.  
 
3 Pusic AL, Cordeiro PG. An accelerated approach to tissue expansion for breast reconstruction: 
experience with intraoperative and rapid postoperative expansion in 370 reconstructions. Plast 
Reconstr Surg. 2003;111(6):1871-5.  
 
4 Cordeiro PG, Jazayeri L. Two-stage implant-based breast reconstruction: an evolution of the 
conceptual and technical approach over a two-decade period. Plast Reconstr Surg. 
2016;138(1):1-11.  
 
5 Hsieh F, Lam TC. Evaluation of AirXpanders for breast reconstruction: early experience from 
Sydney. Plast Reconstr Surg Glob Open. 2015;3(8):e495.  
 
6 American Society of Anesthesiologists (ASA). ASA Physical Status Classification System. 
Accessed 7/9/2016. Available at: https://www.asahq.org/resources/clinical-information/asa-
physical-status-classification-system.  
 
7Cordeiro PG, McCarthy CM. A Single Surgeon’s 12-year Experience with Tissue 
Expander/Implant Breast Reconstruction: Part I. A Prospective Analysis of Early Complications. 
Plast Reconstr Surg. 2006;118(4):825-31.

Protocol Version # 2 
21 
 
APPENDICES 
APPENDIX A: Participant Eligibility Checklist  
A Participant Eligibility Checklist must be completed in its entirety for each subject prior to 
registration. The completed, signed, and dated checklist must be retained in the patient’s study 
file and the study’s Regulatory Binder.  
 
The study coordinator, treating physician and an independent reviewer must verify that the 
participant’s eligibility is accurate, complete, and legible in source records. A description of the 
eligibility verification process should be included in the EPIC or other Electronic Medical 
Record progress note.  
 
The following is an example of a Participant Eligibility checklist template.  Modify this 
checklist to fit your study and include it in the appendix section of your protocol document.  The 
protocol-specific checklist is required by the SRC and must be approved by the IRB.  
 
Protocol Title: 
      
Applying New Device Technologies for Tissue 
Expander/Implant-Based Breast Reconstruction 
Protocol Number: 
36748 
Principal Investigator: 
Dr. Dung Nguyen 
 
II. Subject Information: 
 
Subject Name/ID: 
 
Gender:    
 Male     
 Female 
III. Study Information: 
SRC Approved 
 IRB Approved 
 Contract signed 
 
IV. Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation* 
1. Diagnosis of breast cancer or reason for 
prophylactic mastectomy (e.g., BRCA 
mutation and/or strong family history of 
breast cancer), both unilateral and bilateral 
mastectomy.  
 
 
      
2. No prior breast surgery (excluding biopsy 
and lumpectomy) or breast radiation 
 
 
      
3. Women age 18 years or older, no race-
ethnic restrictions 
 
 
      
4. Ability to understand and willingness to 
sign written informed consent document 
 
 
      

Protocol Version # 2 
22 
 
5. No life expectancy restrictions 
 
 
      
6. ECOG or Karnofsky Performance Status 
will not be employed 
 
 
      
7. No requirements for organ and marrow 
function 
 
 
      
Exclusion Criteria 
(From IRB approved protocol) 
 
1. Recent steroid use 
 
 
      
2. No major medical comorbidities (defined as 
ASA III or greater)   
 
 
      
3. No connective tissue disorder 
 
 
      
4. Prior breast surgery, excluding biopsy and 
lumpectomy 
 
 
      
5. History of or plan for breast radiation 
 
 
      
6. Pregnant and nursing patients 
 
 
      
7. No restrictions regarding use of other 
Investigational Agents 
 
 
      
8. No exclusion criteria related to history of 
allergic reactions 
 
 
      
9. No exclusion criteria relating to 
concomitant medications or substances that 
have the potential to affect the activity or 
pharmacokinetics of the study agent, except 
as per #1 
 
 
      
10. No other agent-specific exclusion criteria 
 
 
      
11. No exclusion of cancer survivors or those 
who are HIV-positive 
 
 
      
*All subject files must include supporting documentation to confirm subject eligibility.  
The method of confirmation can include, but is not limited to, laboratory test results, 
radiology test results, subject self-report, and medical record review.   
IV.  Statement of Eligibility 
By signing this form of this trial I verify that this subject is [
 eligible / 
 ineligible] for 
participation in the study. This study is approved by the Stanford Cancer Institute Scientific 
Review Committee, the Stanford IRB, and has finalized financial and contractual agreements as 
required by Stanford School of Medicine’s Research Management Group.   
 
 
 
Treating Physician Signature: 
Date: 
Printed Name: 
 

Protocol Version # 2 
23 
 
 
Secondary Reviewer Signature: 
Date: 
Printed Name: 
 
 
Study Coordinator Signature: 
Date: 
Printed Name: