Breast Reconstruction With Acellular Dermal Matrix in the Setting of Breast Cancer Treatment

Study Overview
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Brief Summary
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To evaluate breast reconstruction with implants using biological mesh (Strattice™) in the setting of breast cancer treatment.

Detailed Description
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OBJECTIVES: To evaluate the outcome of immediate breast reconstruction with Acellular Dermal Matrix (Strattice™), measuring safety, effectiveness, and costs. The primary outcome measure is number of unplanned surgical procedures. STUDY DESIGN: A prospective randomized multicenter trial. One hundred and twenty patients with breast cancer will be enrolled into the study. Study duration will be two years from time of primary cancer surgery. TRIAL DESIGN This is a randomized controlled multicenter trial, comparing IBR without (group A) and with (group B) the use of ADM. Participants eligible for the study are patients with breast cancer, planned for mastectomy, who wishes IBR with implants. Each participant is individually randomized to either be reconstructed using implants with total submuscular coverage (A) or reconstruction with ADM and partial muscle coverage (B). Method of assigning patients to treatment groups: After signing and dating the informed consent the patient is entered into the study. If all inclusion and none of the exclusion criteria are full filled, the patient will be randomized to group A or group B. TREATMENT/ INTERVENTION The decision and treatment plan advocating mastectomy is based on multi disciplinary conference (MDT), and the diagnosis of invasive or pre-invasive (in situ) breast cancer is made on triple assessment. If the patient wishes to undergo immediate implant based reconstruction, and meets the selection criteria for entering the study, she is randomly selected to be treated according to Group A or Group B. Group A will be reconstructed with expander or anatomical gel implant without ADM, using complete muscle coverage. Group B will be reconstructed with expander or anatomical gel implant using partial muscle coverage in conjunction with ADM. Randomization at enrollment is made with regard to the use of ADM or not, so both expander and direct-to-implant techniques will be utilized in both groups, depending on the quality of skin flaps at time of surgery. RANDOMIZATION TYPE Patients will be allocated to treatment according to permuted block technique. The actual randomization will be performed using computer based system located at Regional Cancer Center (RCC) within Karolinska Institutet. In this system inclusion and exclusion criteria will be automatically checked before patients are randomized to treatment. The randomization process will be stratified for the participating units. STATISTICAL METHODS The main endpoint to be analyzed is the proportion of unplanned reoperations after the initial breast reconstruction. The difference in proportions between the two groups will be presented as a difference in proportion together with a 95% confidence interval. Differences will be tested using Fishers Exact Test. Logistic regression will be used to take into account possible confounding factors. STUDY MANAGEMENT Data recording: The investigators will ensure that all data from patient visits are entered promptly in ink, in the case report forms (CRF). The principal investigator must sign the final CRF page to attest to the accuracy and completeness of the data. The data from the CRFs are then transferred to a database. Monitoring and audit: At periods not exceeding 3 months, centers will be contacted to discuss the progress of the trial, with the purpose to verify CRF data against source records for accuracy of data recording and collection.

Official Title
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Immediate Breast Reconstruction With or Without the Use of Acellular Dermal Matrix: A Randomized Controlled Multicenter Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: Reconstruction with ADM.
* Procedure: Skin or nipple sparing mastectomy
* Procedure: Reconstruction with implant
* Procedure: Total submuscular coverage
* Procedure: Partial submuscular coverage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with invasive or pre-invasive (in situ) breast cancer, planned for immediate breast reconstruction post-skin sparing or nipple sparing mastectomy (unilateral or bilateral) Patient agrees to participate in study and to sign an informed consent form Able and willing to return for all scheduled and required study visits Exclusion Criteria: Is a smoker (patient having quit at least 4 weeks prior surgery can be included) BMI <18 or > 30 Previous radiation therapy to the region at any time Insulin-dependent diabetes or any immune deficiency requiring immunosuppressant use such as cortisone or biological therapies Predicted implant size <200 or >600 ml per investigator assessment Allergy to porcine Pregnancy or lactating Current enrollment or plans to enroll in another clinical trial unless a retrospective study Neoadjuvant treatment with chemotherapy

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast reconstruction with ADM<br>Implant based Breast Reconstruction with ADM. Both arms will undergo skin or nipple sparing mastectomy and immediate breast reconstruction with implants. Patients in group B with ADM and partial submuscular coverage. | Procedure: Reconstruction with ADM.<br>* If the patient wishes to undergo immediate implant based reconstruction, and meets the selection criteria for entering the study, she is randomly selected to be treated according to Group A or Group B. Group A (no intervention) will be reconstructed with expander or anatomical gel implant without ADM, using complete muscle coverage. Group B (Intervention) will be reconstructed with expander or anatomical gel implant using partial muscle coverage in conjunction with ADM.<br>* Other names: Breast reconstruction;Procedure: Skin or nipple sparing mastectomy<br>* Mastectomy for invasive or pre-invasive breast cancer<br>* Other names: Implant;Procedure: Reconstruction with implant<br>* Immediate breast reconstruction with implant<br>* Other names: Breast cancer;Procedure: Partial submuscular coverage<br>* Implant based breast reconstruction with partial submuscular coverage<br>|
| Active Comparator: Breast reconstruction without ADM<br>Breast reconstruction without ADM. Both arms will undergo skin or nipple sparing mastectomy and immediate breast reconstruction with implant. Patients in group B will be reconstructed with implant and total submuscular coverage. | Procedure: Skin or nipple sparing mastectomy<br>* Mastectomy for invasive or pre-invasive breast cancer<br>* Other names: Implant;Procedure: Reconstruction with implant<br>* Immediate breast reconstruction with implant<br>* Other names: Breast cancer;Procedure: Total submuscular coverage<br>* Implant based breast reconstruction with total submuscular coverage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of this study is number of unplanned/ unanticipated surgical breast procedures. Other endpoints in the trial will be secondary. | Follow-up time after primary surgery is 24 months. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aesthetic outcome | To measure aesthetic outcome between the two study groups using a 6- point scale. The evaluation will be done by three independent groups consisting of lay people, professionals (breast/ plastic surgeons) and patient evaluation. The aesthetic evaluation will be based on the pre and postoperative photos. | 24 months | 
| Complications | To measure any difference between the two study groups in complication rates. | 24 months | 
| Number of surgical procedures | To compare the total number of surgical procedures (planned or unplanned) between the two study groups). | 24 months | 
| Cost-Benefit analysis | A cost-benefit analysis comparing the cost for an IBR with implant without ADM, vs. IBR with ADM (Strattice™) during a 24 months follow-up time. | 24 months | 
| Quality of Life | Measure Quality of Life in both groups, using the EORTC QLQ-C30 (Generic tool), EORTC-BR23 (Breast cancer specific tool), EORTC-BRR (Specific for breast reconstruction). | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBR, Strattice, Breast reconstruction, Immediate breast reconstruction, Acellular dermal matrix, Biological mesh, Randomized controlled trial, Breast cancer, Implants, Mastectomy, Direct-to-implant, ADM, RCT