Safety and Feasibility Study of the CELLSPAN Esophageal Implant (CEI) in Patients Requiring Short Segment Esophageal Replacement
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Cohort 1: The number of patients who develop continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and visual endoscopic evaluation.
研究概览
简要总结
Cellspan™ Esophageal Implant-Adult (CEI)
The CEI is a combination product consisting of an engineered synthetic scaffold (device constituent) seeded and cultured with the patient's adipose derived mesenchymal stem cells (biologic constituent), intended to stimulate regeneration of a structurally intact, living biologic esophageal conduit, in patients requiring full circumferential esophageal reconstruction up to 6 cm segment in length.
This is a dual arm, unblinded, multicenter, prospective first-in-human (FIH) feasibility study to be performed at a maximum of 5 centers in the United States with a maximum of 10 subjects in total. All subjects will be followed for a minimum of 2 years post-implant surgery.
Since this is an FIH experience, the study will utilize an independent Data Monitoring Committee (DMC) to evaluate safety on a continuous basis to mitigate any safety risks to subjects. A sentinel approach to enrollment of subjects shall be guided by the DMC review of cases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject ≥18 years of age
- •The patient has medical conditions requiring esophageal reconstruction, such as, but not limited to:
- •Refractory benign esophageal strictures (RBES)
- •Esophageal perforation (full thickness)
- •Chronic/persistent esophageal fistula
- •Combination of esophageal perforations/fistula with RBES
- •The patient must have failed at least 3 previous treatment modalities to correct the medical esophageal condition (a-d).
- •a. If RBES: i. Steroid treatment ii. Esophageal balloon dilation (EBD) iii. Stent use ≥ 6 months iv. Endoscopic incisional repair
- •b. If esophageal perforation: i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use ≥ 6 months iv. Primary surgical repair
- •c. If Chronic/Persistent fistula(e): i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent ≥ 6 months iv. Primary surgical repair
- •d. If Combination Perforation/fistula with RBES i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use ≥ 6 months iv. Primary surgical repair
- •The patient must be a surgical candidate for a short segment esophageal reconstruction (≤6 cm full circumferential segmental excision)
- •The location of the esophageal segment for surgical resection is within the thoracic cavity, defined as, above the diaphragm and at least 4 cm below the larynx.
- •The patient must be a high-risk candidate for minimally invasive esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery, due to a medical contraindication
- •All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to restore a patent durable biologic esophageal conduit
- •The patient/guardian is willing and able to comply with the protocol specified medication regimen and follow-up evaluations
- •The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)
- •Inclusion Criteria Cohort 2:
- •Subject ≥18 years of age
- •The patient has medical conditions requiring esophageal reconstruction, limited to:
- •a. Spit Fistula with an upper esophageal ostomy in the neck
- •Patients may require esophageal de-functioning with a resulting cervical spit fistula if they are not candidates for immediate esophageal reconstruction. This may occur for multiple reasons, including being too sick for reconstruction, healing of the airway after tracheo-esophageal fistula repair, requirement for further therapy prior to reconstruction, or recovering from sepsis due to esophageal perforation.
- •The patient must be a surgical candidate for a short segment esophageal reconstruction (< 7cm), a full circumferential segmental esophageal extension in order to have sufficient length to make the anastomosis to the distal thoracic esophagus, to a gastric or to an intestinal interposition conduit that will re-establish oral nutritional intake. i.
- •Patient must be a high-risk candidate for the standard of care treatment of esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus following the CEI subdermal extension procedure and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery.
- •All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to mature in the subdermal area prior to mobilization
- •The patient/guardian is willing and able to comply with the protocol- specified medication regimen and follow-up evaluations
- •The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).
排除标准
- •all cohorts:
- •Subject requires or undergoes an esophageal segmental excision >6 cm in length
- •Esophageal segment extends below the diaphragm or <4 cm below larynx
- •Pre-existing implants/structures adjacent to target surgical location for implant that could cause abrasion of the scaffold/regenerated tissue (e.g., pacemaker lead, vascular clips, vascular grafts).
- •Known clinical contraindication that would obfuscate the use of the covered metallic stent to be used as an adjunct to the procedure
- •Post ablation stricture for Barrett's esophagus treated less than 1 year prior to planned procedure
- •Patient has a comorbidity or contraindication that would preclude any study required procedures including adipose tissue biopsy and esophageal resection surgery. Comorbidities are defined from a subset of the Charlson Comorbidities Index (CCI, Yamashita 2018) scoring system and include:
- •diabetes mellitus (CCI = 1)
- •connective tissue disorders (CCI=1)
- •immune compromised
- •chemotherapy radiotherapy or chemoradiotherapy (within 60 day clearance)
- •inability to tolerate major thoracotomy
- •active infection at the biopsy or thoracotomy incision site
- •peripheral vascular disease (CCI=1)
- •all patients with a CCI> 2
- •Life expectancy of less than 1 year
- •Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7days prior to index procedure.
- •Has a known untreated neurological, psychological, psychiatric, or other disorder that would interfere with trial endpoints or with cooperation with the requirements of the trial
- •Has a diagnosis of immunodeficiency, receiving cancer therapy including chimeric antigen receptor T cells (CAR-T), receiving systemic steroid therapy (>10 mg prednisone or equivalent daily dose), or any other form of pharmacologic therapy that would inhibit the intended cell growth (e.g., protease inhibitors, immunosuppressants, anti-cytokine therapies) within 30 days prior to index procedure or intended for use during any time after implantation through 12 months post-index procedure.
- •Patient with an infection requiring antibiotic therapy
- •Known allergy to Nitinol (for adjunctive self-expanding covered metallic stent procedure)
- •Current participation in another investigational drug or device study
- •Patient is a prisoner
- •If in the opinion of the investigator, the patient requires pain management (potentially opioid medications) as a result of study participation, the patient is at an unreasonable risk of addiction. This decision may be based upon medical or social history, personal situation, or the expected time course, length, and type of medication use.
研究组 & 干预措施
Short Segment Esophageal Replacement in patients requiring a full reconstruction of the esophagus
干预措施: CEI Thoracic Surgical Implantation-Cellspan™ Esophageal Implant-Adult (CEI) in patients requiring a full reconstruction of the esophagus (Combination Product)
Short Segment Esophageal Replacement in patients that have had a previous partial esophagectomy
干预措施: CEI Extra-Thoracic Subdermal Surgical Implantation - Cellspan™ Esophageal Implant-Adult (CEI) in patients that have had a previous partial esophagectomy (Combination Product)
结局指标
主要结局
Cohort 1: The number of patients who develop continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and visual endoscopic evaluation.
时间窗: Month 3
The number of patients who develops continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and visual endoscopic evaluation, prior to or at Month 3 visit (Day 77 ±10) following implantation.
All Cohorts: The number of patients who does not develop anastomotic leak or fistula that requires non-endoscopic therapy.
时间窗: 42 days
The number of patients who does not develop anastomotic leak or fistula that requires non-endoscopic therapy.
All Cohorts: The number of patients within the first 42 days that do not require a fall back emergency esophagectomy procedure
时间窗: 42 days
The number of patients within the first 42 days that do not require a fall back emergency esophagectomy procedure (gastric pull-up, colonic interposition, or other surgical reconstruction).
All Cohorts: Number of participants experiencing death within 30 days of index procedure
时间窗: Within 30 days
Number of participants experiencing death within 30 days of index procedure
Cohort 2: The number of patients with maturation of the CEI graft under the dermal layer followed by mobilization and connection to the distal esophagus within the thoracic cavity to form a continuous biologic neo-conduit based on endoscopic evaluation
时间窗: Month 3
The number of patients with maturation of the CEI graft under the dermal layer followed by mobilization and connection to the distal esophagus within the thoracic cavity to form a continuous biologic neo-conduit based on endoscopic evaluation
次要结局
未报告次要终点