First-in-human, Study of MATTISSE® Tissue Engineering Chamber in Adult Female Patients Undergoing Breast Reconstruction After Mastectomy for Cancer (TIDE)

First-in-human Study of MATTISSE® Tissue Engineering Chamber in Adult Female After Total Mastectomy for Breast Cancer in Immediate or Delayed 2-stage Tissue Expander Reconstruction or Conversion From Implant-based to Autologous Reconstruction

This study is a first in human, two-stage single arm non-comparative study of safety and performance.

The aim of the study is to asses the safety and the clinical performance of a new device : the MATTISSE tissu engineering chamber.

Study Overview

• Status: Recruiting
• Conditions: Breast Reconstruction; Breast Cancer Female; Breast Cancer Prevent
• Intervention / Treatment: Device: MATTISSE TEC

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre GUERRESCHI, Pr; Phone Number: 03.20.44.56.59; Email: clinic@lattice-medical.com

Study Locations

• France
  • Strasbourg, France, 67091
    • Recruiting
    • CHU de Strasbourg
    • Contact: Frédéric BODIN, Pr
  • Nord
    • Lille, Nord, France, 59000
      • Recruiting
      • Hospital of Lille
      • Contact: Pierre Guerreschi, Prof.
• Georgia
  • Tbilissi, Georgia, 0159
    • Recruiting
    • Institute of Clinical Oncology
    • Contact: Gia NEMSADZE, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Criteria related to pathology:

• Female patient over 18 Years old

• Patient who required autologous breast reconstruction:

  • Immediate unilateral reconstruction after total mastectomy for early-stage breast cancer
  • Breast reconstruction after unilateral preventive total mastectomy
  • or delayed unilateral reconstruction after total mastectomy for early-stage breast cancer with a tissue expander implantation
  • or conversion from implant-based to autologous reconstruction: Patient who had a breast implant during a previous reconstruction after total mastectomy for cancer, and who needs to change it.
• For patient with active cancer: Patient with early-stage cancer (stage 0, I or II, with tumor size < 50mm, without lymph-node involvement) needing oncological management that does not required radiotherapy after surgery on the breast area or on the flap donor site
• Patient who required Nipple sparing (NSM) or Skin sparing mastectomy (SSM) with a unique surgical approach (same for mastectomy and implant) insertion; or implant removal for patient undergoing autologous conversion, or expender removal for patient undergoing differed reconstruction.
• Autologous reconstruction using Lateral Intercostal Perforator (LICAP) flap or an intercostal thoracic artery perforation flap (LTAP) if oncological conditions do not allow for LICAP harvesting.
• Patient medically fit for surgery without significant comorbidities
• Breast cup-size less than D
• Body mass index >20 kg/m2 or patient for whom sufficient flap volume is expected according to surgeon's assessment
• Adequate hematopoietic functions

Criteria related to population:

• Subjects who have given free, informed and written consent to participate in the study;
• Patient able to answer questionnaires, able to communicate in the language of the study country;
• Subjects affiliated to a social security schema or entitled to a social security scheme.

Non-inclusion Criteria:

Pathology related criteria:

• Patient undergoing bilateral reconstruction
• Patient undergoing bilateral preventive mastectomy
• Patient undergoing simultaneous contralateral breast reduction, mastopexy, and augmentation
• Previous history of radiotherapy on the breast area or on the flap donor site
• Previous history of breast or axillary surgery that does not allow fat flap dissection
• Presence of pacemaker or metallic prosthesis making patient unsuitable for MRI
• Body mass index >30 kg/m2
• Taking medication for weight loss at the time of inclusion visit
• Presence of major medical conditions that may compromise patient's health and healing
• Diabetes and a history of gestational diabetes
• Active smoking
• Microangiopathy, Vascular history and all systemic disease (systemic Raynaud's disease)
• Patient with intertrigo or infection or alteration of the surgical site confirmed pre-operatively by clinical examination
• Allergy to anesthetics or contrast media
• Immunocompromised patient (HIV) or patient used immunosuppressants

Population related criteria

• Pregnant patient
• or breastfeeding patient or woman who has nursed a child three months within inclusion
• Participation in a clinical trial in the 3 months prior to the initial visit
• Predicted unavailability during study.
• Patient deprived of liberty or under guardianship.
• Patient unable to give consent

Medical device related criteria

• Allergy to any of the components of the medical device.

EXCLUSION CRITERIA

• Positive or suspicious extemporaneous sentinel node biopsy
• Non integrity of LICAP and LTAP vessels, showed by the pre-operative doppler
• Patient not yet implanted with MATTISSE®, whose cancer stage will finally require radiotherapy treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: MATTISSE TEC; Patient included receive MATTISSE TEC	Device: MATTISSE TEC; Tissue engineering chamber MATTISSE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance objective: To assess the efficacy at 6 months post-operation of breast reconstruction using MATTISSE® breast implants in patients undergoing breast reconstitution after total mastectomy surgery for cancer.	Success is defined as: Tissue expansion (flap enlargement) from implantation up to 6 months post operation --> A 50% increase in the expanded size at 6 months compared to initial size flap is considered as a success. Indeed, the optimal growth of the flap is expected at 6 months,; Tissue expansion will be assessed using MRI at discharge (after surgery) and 6 months post operative. The volume of flap at 6 months will be compared to the flap size initially implanted. All MRI imaging will be assessed by and independent expert radiologist. Failure is defined as: less than 50% increase in the expanded size at 6 months compared to initial size flap MATTISSE® Prothesis removal	6 months post-surgery
Safety objective: To assess the 6 months surgical complications rate of MATTISSE® TEC implant-based immediate breast reconstruction. Adverse events will be recorded.	Minor complications include: Superficial skin necrosis that requires only debridement; Flap necrosis; Subcutaneous hematoma: any hematoma requiring surgical exploration; Inflammatory reaction; Seroma: defined as that which requires echo-guided puncture at least once after drain removal.; Pain; Delayed wound healing/wound dehiscence: any wound healing problems, detected during clinical examination and not requiring an intervention; Implant malposition; Superficial Venous Thrombosis (Mondor disease); Capsular contracture Major complications include: All complications that lead to MATTISSE® TEC removal:; Skin necrosis leading to implant exposure; Infection; Implant malposition leading to implant exposure; Device failure or defect: when the implant breaks or collapses, e.g., the base separates from the shell, failure at the time of surgical placement (fracture of the TEC before placement); Granuloma.	6 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of tissue expansion (flap enlargement) from implantation up to 36 months post operation.	Tissue expansion will be assessed using MRI at discharge (after surgery), 12, 24 and 36 months post operative. All MRI imaging will be assessed by and independent expert radiologist.	Surgery visit, 3, 6, 12, 24 and 36 months post-intervention
Evolution of breast softness from inclusion to 36 months	The breast softness will be assessed by investigator surgeon and patients themselves at discharge (after surgery), 3, 6 ,12, 24 and 36 months as:; Stage 1: Breast is soft; Stage 2: Breast is hard; Stage 3: Breast is hard with distortion; Stage 4: Breast is hard, painful with distortion	Surgery visit, 3, 6, 12, 24 and 36 months post-intervention
Evolution of MATTISSE® TEC resorption until 36 months follow up: the resorption is active between 6 and 12 months after surgery.	MATTISSE® TEC resorption will be observed quantitatively on MRI achieved at 3, 6, 12, 24 and 36 months associated with the touch of the surgeon and patients feeling. The TEC resorption will be classified as: Absent: no resorption at all.; Small resorption: TEC has been reabsorbed a little bit compared to the initial; Great resorption: TEC has been absorbed a lot but not totally; Total: Shell and base are no longer visible on the MRI and not felt by the surgeon	Surgery visit, 3, 6, 12, 24 and 36 months post-intervention
The volume of the reconstructed breast compared to the volume of the contralateral one at 12, 24 and 36 months	At 12, 24 and 36 months, we will assess during physical examinations, the volume of the reconstructed breast and the volume of the contralateral one.	3, 6, 12, 24 and 36 months post surgery
Aesthetic breast appearance before and after surgery using photo	Aesthetic breast appearance will be assessed before surgery, 6 at 12, 24 and 36 months post-surgery using standardized photographs. The assessment will be done by the surgeon and 2 independent external specialists who validated standardized photographs. The following scoring points will be used: Excellent: Treated breast nearly identical to that before surgery; Good: Treated breast slightly different to that before surgery; Fair: Treated breast clearly different to that before surgery but not seriously distorted; Poor: Treated breast seriously distorted compared to that before surgery	3, 6, 12, 24 and 36 months post surgery
The maintain of breast (i.e., flap) volume stability at 12, 24 and 36 months compared to that at 6 months	Flap volume at 12, 24 and 36 months is compared at that assessed at 6 months using MRI. All MRI imaging will be assessed by and independent expert radiologist.	3, 6, 12, 24 and 36 months post surgery
The impact of the flap transfer on the donor site assessed at surgery, 3, 6, 12, 24 and 36months post-surgery	Impact of the flap transfer on the donor site will be assessed at surgery, 3, 6, 12, 24 and 36 months post-surgery using different parameters: Tissue necrosis (Yes/ No); Symmetry of the donor site area (comparing to the other side of the patient): Yes/ No	3, 6, 12, 24 and 36 months post surgery
Pain (VAS)	Pain score will be assessed at inclusion, discharge, 3, 6, 12, 24 and 36 month using a 10 Visual Analogue Scale [VAS, 0 (no pain) and 10 (worst possible pain)]	3, 6, 12, 24 and 36 months post surgery
The quality of life and the satisfaction of patients	Quality of life and patients' satisfaction will be done through the BREAST-Q© questionnaire (module of reconstruction pre and post-surgery version) at inclusion and at 3, 6 and 12 months post operative. The quality of life is evaluated through 2 scales (psychological well-being and physical well-being: breast). The satisfaction is evaluated with 1 scale : (satisfaction with breast).	3, 6, 12, 24 and 36 months post surgery
Surgeon satisfaction regarding the use of MATTISSE® TEC and implantation procedure.	- Surgeons' satisfaction regarding the use of MATTISSE® TEC and implantation procedure will be assessed on: Global satisfaction of the surgeon (5 points Likert scale); Ease of use; Material ergonomics; Ease of insertion; Ease of fixing	Visit 2, surgery
Evolution of biological parameters up to 6 months after surgery	Complete blood counts evolution will be assessed at inclusion, at discharge, and at 3 and 6 months post-implantation, by measuring Hemoglobin , leukocytes Lymphocyte rate Neutrophil rate and Thrombocytes Units: Hemoglobin : g/L; leukocytes :10⁹/L; Lymphocyte rate : %; Neutrophil rate : %; Thrombocytes : 10⁹/L	Inclusion, Discharge, 3, 6 months post-intervention
Evolution of biological parameters up to 6 months after surgery	C-reactive protein evolution will be assessed at inclusion, at discharge, and at 3 and 6 months post-implantation, by measuring CRP Unit: - CRP : nmoL/L	Inclusion, Discharge, 3, 6 months post-intervention
Evolution of biological parameters up to 6 months after surgery	Total protein evolution will be assessed at inclusion, at discharge, and at 3 and 6 months post-implantation, by total protein assay Unit: Total protein: Normal or Not normal	Inclusion, Discharge, 3, 6 months post-intervention
Evolution of biological parameters up to 6 months after surgery	Protein electrophoresis will be assessed at inclusion, at discharge, and at 3 and 6 months post-implantation, by performing protein electrophoresis. Unit : Protein electrophoresis: Normal or Not normal	Inclusion, Discharge, 3, 6 months post-intervention
Safety up to 36 months post operation	Safety up to 36 months, will be assessed by measuring the complication rate after breast reconstruction using MATTISSE® TEC. Adverse events up to 36 months post operation will be recorded.	Surgery visit, 3, 6, 12, 24 and 36 months post-intervention

Collaborators and Investigators

• Sponsor: Quanta Medical
• Collaborators: Lattice Medical

Publications and helpful links

General Publications

• Findlay MW, Dolderer JH, Trost N, Craft RO, Cao Y, Cooper-White J, Stevens G, Morrison WA. Tissue-engineered breast reconstruction: bridging the gap toward large-volume tissue engineering in humans. Plast Reconstr Surg. 2011 Dec;128(6):1206-1215. doi: 10.1097/PRS.0b013e318230c5b2.
• Matsuda K, Falkenberg KJ, Woods AA, Choi YS, Morrison WA, Dilley RJ. Adipose-derived stem cells promote angiogenesis and tissue formation for in vivo tissue engineering. Tissue Eng Part A. 2013 Jun;19(11-12):1327-35. doi: 10.1089/ten.TEA.2012.0391. Epub 2013 Mar 28.
• Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, Ruddy K, Tsang J, Cardoso F. Breast cancer. Nat Rev Dis Primers. 2019 Sep 23;5(1):66. doi: 10.1038/s41572-019-0111-2.
• Schmauss D, Machens HG, Harder Y. Breast Reconstruction after Mastectomy. Front Surg. 2016 Jan 19;2:71. doi: 10.3389/fsurg.2015.00071. eCollection 2015.
• Tzafetta K, Ahmed O, Bahia H, Jerwood D, Ramakrishnan V. Evaluation of the factors related to postmastectomy breast reconstruction. Plast Reconstr Surg. 2001 Jun;107(7):1694-701. doi: 10.1097/00006534-200106000-00009.
• Vega S, Smartt JM Jr, Jiang S, Selber JC, Brooks CJM, Herrera HR, Serletti JM. 500 Consecutive patients with free TRAM flap breast reconstruction: a single surgeon's experience. Plast Reconstr Surg. 2008 Aug;122(2):329-339. doi: 10.1097/PRS.0b013e31817f45cb.
• Duggal CS, Grudziak J, Metcalfe DB, Carlson GW, Losken A. The effects of breast size in unilateral postmastectomy breast reconstruction. Ann Plast Surg. 2013 May;70(5):506-12. doi: 10.1097/SAP.0b013e318263f1f8.
• Noone RB. Thirty-five years of breast reconstruction: eleven lessons to share. Plast Reconstr Surg. 2009 Dec;124(6):1820-1827. doi: 10.1097/PRS.0b013e3181bf821a. No abstract available.
• Salzberg CA, Ashikari AY, Koch RM, Chabner-Thompson E. An 8-year experience of direct-to-implant immediate breast reconstruction using human acellular dermal matrix (AlloDerm). Plast Reconstr Surg. 2011 Feb;127(2):514-524. doi: 10.1097/PRS.0b013e318200a961.
• Morrison WA, Marre D, Grinsell D, Batty A, Trost N, O'Connor AJ. Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering. EBioMedicine. 2016 Apr;6:238-245. doi: 10.1016/j.ebiom.2016.03.032. Epub 2016 Mar 23.
• Petit JY, Rietjens M, Lohsiriwat V, Rey P, Garusi C, De Lorenzi F, Martella S, Manconi A, Barbieri B, Clough KB. Update on breast reconstruction techniques and indications. World J Surg. 2012 Jul;36(7):1486-97. doi: 10.1007/s00268-012-1486-3.
• Cordeiro 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 Sep 15;118(4):825-831. doi: 10.1097/01.prs.0000232362.82402.e8.
• Martindale V, Menache A. The PIP scandal: an analysis of the process of quality control that failed to safeguard women from the health risks. J R Soc Med. 2013 May;106(5):173-7. doi: 10.1177/0141076813480994. No abstract available.
• Mian R, Morrison WA, Hurley JV, Penington AJ, Romeo R, Tanaka Y, Knight KR. Formation of new tissue from an arteriovenous loop in the absence of added extracellular matrix. Tissue Eng. 2000 Dec;6(6):595-603. doi: 10.1089/10763270050199541.
• Tanaka Y, Tsutsumi A, Crowe DM, Tajima S, Morrison WA. Generation of an autologous tissue (matrix) flap by combining an arteriovenous shunt loop with artificial skin in rats: preliminary report. Br J Plast Surg. 2000 Jan;53(1):51-7. doi: 10.1054/bjps.1999.3186.
• Hofer SO, Knight KM, Cooper-White JJ, O'Connor AJ, Perera JM, Romeo-Meeuw R, Penington AJ, Knight KR, Morrison WA, Messina A. Increasing the volume of vascularized tissue formation in engineered constructs: an experimental study in rats. Plast Reconstr Surg. 2003 Mar;111(3):1186-92; discussion 1193-4. doi: 10.1097/01.PRS.0000046034.02158.EB.
• Cronin KJ, Messina A, Knight KR, Cooper-White JJ, Stevens GW, Penington AJ, Morrison WA. New murine model of spontaneous autologous tissue engineering, combining an arteriovenous pedicle with matrix materials. Plast Reconstr Surg. 2004 Jan;113(1):260-9. doi: 10.1097/01.PRS.0000095942.71618.9D.
• Findlay MW, Messina A, Thompson EW, Morrison WA. Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year: an update. Plast Reconstr Surg. 2009 Oct;124(4):1077-1084. doi: 10.1097/PRS.0b013e3181b59ff6.
• Faglin P, Gradwohl M, Depoortere C, Germain N, Drucbert AS, Brun S, Nahon C, Dekiouk S, Rech A, Azaroual N, Maboudou P, Payen J, Danze PM, Guerreschi P, Marchetti P. Rationale for the design of 3D-printable bioresorbable tissue-engineering chambers to promote the growth of adipose tissue. Sci Rep. 2020 Jul 16;10(1):11779. doi: 10.1038/s41598-020-68776-8.
• Gradwohl M, Chai F, Payen J, Guerreschi P, Marchetti P, Blanchemain N. Effects of Two Melt Extrusion Based Additive Manufacturing Technologies and Common Sterilization Methods on the Properties of a Medical Grade PLGA Copolymer. Polymers (Basel). 2021 Feb 14;13(4):572. doi: 10.3390/polym13040572.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 3121_MATFIH22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No