Mastectomy and Breast Reconstruction
Conditions
Keywords
Breast reconstruction, Breast implant, Breast cancer, Mastectomy
Brief summary
The purpose of this study was to compare the efficacy of immediate single-stage post-mastectomy breast reconstruction with Strattice Reconstructive Tissue Matrix (Strattice) as compared to immediate two-stage post-mastectomy breast reconstruction where the initially placed expander was exchanged for a breast implant only, without any type of reinforcement.
Detailed description
The primary objective of this study is to compare the efficacy of immediate single-stage post-mastectomy breast reconstruction with Strattice™ TM, otherwise referred to as DTI as compared to immediate two-stage post-mastectomy breast reconstruction where the initially placed expander will be exchanged for a breast implant only, without any type of a reinforcement. The objective will be achieved by prospectively assessing the number of planned and unplanned post-mastectomy surgical interventions within 12 months of the mastectomy. Two-stage breast reconstruction will include the initial placement of a tissue expander in a total or partial submuscular position. In the case of partial muscle coverage, this will be without the support of any mesh or autologous flap to reinforce the lower pole. The expander will be inflated over approximately the next one to six months, and then replaced with an implant.
Interventions
PROCEDUREBreast Reconstruction, Direct to Implant (DTI) with Strattice™
PROCEDURETwo Stage Breast Reconstruction
Sponsors
LifeCell
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female 18 years or older * A candidate for both arms of the study involving immediate breast reconstruction post-skin sparing mastectomy (unilateral or bilateral) DTI with the use of Strattice™ Reconstructive Tissue Matrix (TM), 2 stage with use of Tissue Expander through exchange to Implant without support of a mesh or autologous tissue) * An American Society of Anesthesiologists (ASA) Physical Status Classification of 1 or 2 * Estimated life expectancy \> 3 years * Able and willing to return for all scheduled and required study visits * Able to provide written informed consent for study participation
Exclusion criteria
* Clinically significant systemic disease, as determined by the Investigator, which could affect study participation or study results * Received neo-adjuvant, inductive chemo-therapy (except Herceptin, or other targeted therapy) within 4 weeks prior to mastectomy * Previous radiation therapy to either breast at any time * Predicted permanent implant size that is greater than or equal to 500 grams (gms), per Investigator assessment * Body mass index (BMI) \<17 or \> 30 * Co-morbid factors which predispose to postoperative infection, e.g. diabetes, collagen vascular disease, chronic steroid (except inhalers)/immunosuppressant use, immune deficiency, or co-existent infection * Pregnant or lactating * 3rd degree ptosis * Prior breast surgery including breast reduction, augmentation, mastopexy, quadrectomy, and partial mastectomy with reduction of the skin envelope * Prior use of a device (mesh or matrix) in the Breast * Concomitant unrelated condition of breast/chest wall/skin that, as determined by the investigator, could adversely affect the surgical outcome (e.g. significant chest wall abnormalities including pectus excavatum or pectus carinatum) * Planned autologous tissue flap in addition to prosthetic implant * Use of permanent expander implants such as Becker expanders or the Natrelle™ Permanent expander 150 * Current alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or drug abuse or addiction * Currently enrolled or plans to enroll in another clinical trial unless it is: a registry, a retrospective study, a neo-adjuvant chemotherapy trial (as long as the chemotherapy regimen has been stopped 4 weeks prior to mastectomy), or a hormone/anti-hormonal therapy trial * Any of the conditions identified within the labelled contraindications, i.e. sensitivity to porcine derived products or polysorbate 20.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS) | Up to 12 months post ISS | ISS was defined as the DTI breast reconstruction with Strattice™ or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction. Postmastectomy surgical interventions on the reconstructed breast were reported for each participant and the total number of planned and unplanned post-mastectomy surgical interventions was averaged in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Up to 24 months ppR | The surgeon assessed the level of capsular contracture in the participant's breast using the Baker Breast Contracture Scale where: Grade I=breast is normally soft and looks natural, Grade II=breast is a little firm but looks normal, Grade III=breast is firm and looks abnormal and Grade IV= breast is hard, painful, and looks abnormal. Baker Grade III and IV were defined as clinically significant and are reported here. Data is presented for number of participants with capsular contracture per breast (right breast and left breast). |
| Aesthetic Outcomes of Participants Using Blinded Assessment 2D Photographs by Independent Review Panel | Baseline up to Month 24 | — |
| Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS | Baseline up to 6 months post ISS | ISS was defined as the DTI breast reconstruction with Strattice™ or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction. Postmastectomy surgical interventions on the reconstructed breast were reported for each participant and the total number of planned and unplanned post-mastectomy surgical interventions was averaged in each group. |
| Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast | Within 24 months ppR | Surgical interventions were all planned and unplanned post-mastectomy surgical interventions per participant on the reconstructed breast, within 24 months of the ISS, which is defined as the DTI breast reconstruction with Strattice™ TM or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction. |
| Number of Participants Experiencing One or More Serious Breast Reconstruction-related Complications (BRRC) | Up to 12 months post ISS | Serious BRRC were complications that required re-entry of the breast pocket with or without exchange or removal of the implant and any manipulation of the implant pocket including the infra-mammary fold (IMF). Serious BRRC were detected through review by a medical monitor. Surgical complications included: capsular contracture (Baker grade ≥ 3), infection (local or systemic), hematoma, seroma, inflammation, skin or flap necrosis, implant extrusion, malposition, malrotation, asymmetry, bottoming out. |
| Number of Participants Experiencing One or More Serious BRRC Within 24 Months of Post-Permanent Reconstruction (ppR) | Up to 24 months ppR | Serious BRRC were complications that required re-entry of the breast pocket with or without exchange or removal of the implant and any manipulation of the implant pocket including the IMF. Serious BRRC were detected through review by a medical monitor. BRRC were defined as: a) infection, local or systemic, b) hematoma, c) seroma, d) inflammation, e) skin or flap necrosis, f) capsular contraction as defined by Baker grade \> 3, g) implant extrusion (loss or explants), and h) malposition, malrotation, asymmetry, and bottoming out. |
Other
| Measure | Time frame |
|---|---|
| Time to Return to Work or Normal Daily Activities | 6 and 12 months post-mastectomy and 24 month ppR |
| Health-related Quality of Life | At 3, 6, and 12 months post-mastectomy and at 4 months ppR |
| Healthcare Resource Use Including Length of Hospital Stay and Clinic Visits | At 6 and 12 months post-mastectomy and at 24 months ppR |
Countries
France, Germany, United Kingdom
Participant flow
Pre-assignment details
Out of the 131 enrolled participants, 127 received the study device and were included in the Safety population.
Participants by arm
| Arm | Count |
|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ Participants underwent immediate post-mastectomy breast reconstruction with a breast implant and Strattice™ reconstructive tissue matrix (surgical mesh). | 76 |
| Two Stage Breast Reconstruction Participants underwent immediate, two-stage post-mastectomy breast reconstruction without reinforcement. Initial placement of a tissue expander that was inflated for approximately one to six months, and then replaced with an implant. | 51 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other Miscellaneous Reasons | 0 | 2 |
| Overall Study | Protocol Deviation | 0 | 5 |
| Overall Study | Study Terminated by Sponsor | 1 | 17 |
| Overall Study | Withdrawal by Subject | 2 | 7 |
Baseline characteristics
| Characteristic | Two Stage Breast Reconstruction | Total | Breast Reconstruction, Direct to Implant (DTI) With Strattice™ |
|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 10.4 | 47.9 years STANDARD_DEVIATION 10.56 | 46.8 years STANDARD_DEVIATION 10.58 |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 35 Participants | 86 Participants | 51 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing | 16 Participants | 38 Participants | 22 Participants |
| Race/Ethnicity, Customized Non-Hispanic or non-Latino | 34 Participants | 87 Participants | 53 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 51 Participants | 127 Participants | 76 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 55 |
| other Total, other adverse events | 53 / 76 | 35 / 51 |
| serious Total, serious adverse events | 49 / 76 | 27 / 51 |
Outcome results
Primary
Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS)
ISS was defined as the DTI breast reconstruction with Strattice™ or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction. Postmastectomy surgical interventions on the reconstructed breast were reported for each participant and the total number of planned and unplanned post-mastectomy surgical interventions was averaged in each group.
Time frame: Up to 12 months post ISS
Population: Post-ISS analysis set consisted of all participants who underwent a mastectomy and completed their first reconstruction surgery post-mastectomy and have a valid surgical assessment at least 337 days post ISS (12 month \[365 days\]-4 week \[28 days\] window). Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS) | Unilateral | 1.6 interventions per participant | Standard Deviation 1.87 |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS) | Bilateral | 1.2 interventions per participant | Standard Deviation 1.99 |
| Two Stage Breast Reconstruction | Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS) | Unilateral | 2.2 interventions per participant | Standard Deviation 1.91 |
| Two Stage Breast Reconstruction | Mean Number of Planned and Unplanned Post-mastectomy Surgical Interventions Per Participant on the Reconstructed Breast, Within 12 Months of the Initial Study Surgery (ISS) | Bilateral | 2.3 interventions per participant | Standard Deviation 1.1 |
Secondary
Aesthetic Outcomes of Participants Using Blinded Assessment 2D Photographs by Independent Review Panel
Time frame: Baseline up to Month 24
Population: The independent reviewer panel was not established and data were not collected due to early termination of the study, hence this endpoint could not be analyzed.
Secondary
Number of Participants Experiencing One or More Serious Breast Reconstruction-related Complications (BRRC)
Serious BRRC were complications that required re-entry of the breast pocket with or without exchange or removal of the implant and any manipulation of the implant pocket including the infra-mammary fold (IMF). Serious BRRC were detected through review by a medical monitor. Surgical complications included: capsular contracture (Baker grade ≥ 3), infection (local or systemic), hematoma, seroma, inflammation, skin or flap necrosis, implant extrusion, malposition, malrotation, asymmetry, bottoming out.
Time frame: Up to 12 months post ISS
Population: Post-ISS analysis set consisted of all participants who underwent a mastectomy followed by one of the two implant-based breast reconstruction methods and completed their first reconstruction surgery post-mastectomy and have a valid surgical assessment at least 337 days post ISS (12 month \[365 days\]-4 week \[28 days\] window).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants Experiencing One or More Serious Breast Reconstruction-related Complications (BRRC) | 15 Participants |
| Two Stage Breast Reconstruction | Number of Participants Experiencing One or More Serious Breast Reconstruction-related Complications (BRRC) | 8 Participants |
Secondary
Number of Participants Experiencing One or More Serious BRRC Within 24 Months of Post-Permanent Reconstruction (ppR)
Serious BRRC were complications that required re-entry of the breast pocket with or without exchange or removal of the implant and any manipulation of the implant pocket including the IMF. Serious BRRC were detected through review by a medical monitor. BRRC were defined as: a) infection, local or systemic, b) hematoma, c) seroma, d) inflammation, e) skin or flap necrosis, f) capsular contraction as defined by Baker grade \> 3, g) implant extrusion (loss or explants), and h) malposition, malrotation, asymmetry, and bottoming out.
Time frame: Up to 24 months ppR
Population: ppR Follow-up set consisted of all participants who underwent a mastectomy followed by one of the two implant-based breast reconstruction methods and completed the 24 months ppR visit. Participants whose 24-month visit was performed early due to termination of the study were also included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants Experiencing One or More Serious BRRC Within 24 Months of Post-Permanent Reconstruction (ppR) | 19 Participants |
| Two Stage Breast Reconstruction | Number of Participants Experiencing One or More Serious BRRC Within 24 Months of Post-Permanent Reconstruction (ppR) | 9 Participants |
Secondary
Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR
The surgeon assessed the level of capsular contracture in the participant's breast using the Baker Breast Contracture Scale where: Grade I=breast is normally soft and looks natural, Grade II=breast is a little firm but looks normal, Grade III=breast is firm and looks abnormal and Grade IV= breast is hard, painful, and looks abnormal. Baker Grade III and IV were defined as clinically significant and are reported here. Data is presented for number of participants with capsular contracture per breast (right breast and left breast).
Time frame: Up to 24 months ppR
Population: Safety set included all participants who underwent a mastectomy followed by one of the two implant-based breast reconstruction methods and had their first surgery date recorded. Number analyzed for each category includes those participants for whom the Baker grade was assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Right breast (Grade III) | 0 participants |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Right breast (Grade IV) | 0 participants |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Left Breast (Grade III) | 1 participants |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Left Breast (Grade IV) | 0 participants |
| Two Stage Breast Reconstruction | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Left Breast (Grade IV) | 0 participants |
| Two Stage Breast Reconstruction | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Right breast (Grade III) | 0 participants |
| Two Stage Breast Reconstruction | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Left Breast (Grade III) | 0 participants |
| Two Stage Breast Reconstruction | Number of Participants With Clinically Significant Cases of Capsular Contracture as Defined by Baker Grade III or IV Within 24 Months of ppR | Right breast (Grade IV) | 0 participants |
Secondary
Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast
Surgical interventions were all planned and unplanned post-mastectomy surgical interventions per participant on the reconstructed breast, within 24 months of the ISS, which is defined as the DTI breast reconstruction with Strattice™ TM or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction.
Time frame: Within 24 months ppR
Population: ppR Follow-up set included all participants who underwent a mastectomy followed by one of the two implant-based breast reconstruction methods and completed 24 months ppR visit; whose 24-month visit was performed early due to termination of study were also included. Number analyzed is number of participants with data available at given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast | Unilateral | 2.1 interventions per participant | Standard Deviation 2.04 |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast | Bilateral | 1.6 interventions per participant | Standard Deviation 2.42 |
| Two Stage Breast Reconstruction | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast | Unilateral | 3.0 interventions per participant | Standard Deviation 2.6 |
| Two Stage Breast Reconstruction | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast | Bilateral | 2.8 interventions per participant | Standard Deviation 1.29 |
Secondary
Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS
ISS was defined as the DTI breast reconstruction with Strattice™ or the first surgery of the two-stage breast reconstruction. Data is presented for participants with unilateral (one breast) and bilateral (two breast) reconstruction. Postmastectomy surgical interventions on the reconstructed breast were reported for each participant and the total number of planned and unplanned post-mastectomy surgical interventions was averaged in each group.
Time frame: Baseline up to 6 months post ISS
Population: Safety set included all participants who underwent a mastectomy followed by one of the two implant-based breast reconstruction methods and had their first surgery date recorded. Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS | Unilateral | 1.1 interventions per participant | Standard Deviation 1.43 |
| Breast Reconstruction, Direct to Implant (DTI) With Strattice™ | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS | Bilateral | 1.0 interventions per participant | Standard Deviation 1.76 |
| Two Stage Breast Reconstruction | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS | Unilateral | 1.4 interventions per participant | Standard Deviation 1.4 |
| Two Stage Breast Reconstruction | Number of Planned and Unplanned Post-mastectomy Surgical Interventions of the Reconstructed Breast Within 6 Months of ISS | Bilateral | 0.9 interventions per participant | Standard Deviation 1.28 |
Other Pre-specified
Healthcare Resource Use Including Length of Hospital Stay and Clinic Visits
Time frame: At 6 and 12 months post-mastectomy and at 24 months ppR
Other Pre-specified
Health-related Quality of Life
Time frame: At 3, 6, and 12 months post-mastectomy and at 4 months ppR
Other Pre-specified
Time to Return to Work or Normal Daily Activities
Time frame: 6 and 12 months post-mastectomy and 24 month ppR