A Multi-Center, Double-Blind, Randomized Placebo-Controlled Investigation of Autologous Muscle Derived Cells (AMDC) for the Treatment of Tongue Dysphagia Resulting From the Treatment of Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Study product-related, biopsy procedure-related, and injection procedure-related adverse events.
研究概览
简要总结
The primary objective of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety of AMDC-GIR during the 24 months following 2 consecutive treatments of tongue dysphagia in male and female patients who have undergone surgery and/or chemo- and/or radiotherapy for squamous cell cancer of the oropharynx.
详细描述
The purpose of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety and efficacy of Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) for the treatment of tongue dysphagia (TD) in male and female patients who have undergone surgery and/or chemo- and/or radiotherapy for squamous cell cancer of the oropharynx.
Surgery, chemo- and radiotherapy induce significant TD and result in long-term swallowing dysfunction. The incidence of TD after treatment for cancer of the pharynx exceeds 80%. Therefore, augmenting tongue muscle function may be beneficial to patients. Autologous muscle cell therapy, which involves isolation of cells from skeletal muscle biopsies, ex vivo expansion, and subsequent injection into the tongue, may serve as a durable therapy. In animal studies, muscle derived cells have successfully integrated within tissue to improve tongue strength and function. Intramuscular injection of AMDC-GIR has been shown to produce localized tissue changes at the injection site without a systemic effect. Initial results of a Phase 1 open label trial suggest that 150 x 10⁶ AMDC-GIR for the treatment of TD is safe and may be efficacious. A Phase I/II placebo controlled, randomized clinical trial is warranted.
Patients will receive two treatments of intramuscular injection of 1 AMDC-GIR dose of 150 x 10⁶ cells or identical placebo. For entrance into the study, patients must meet the study inclusion criterion and must not meet any of the exclusion criteria. Patients will have quantitative and qualitative measures of swallowing impairment assessed before treatment and at prescheduled intervals after treatment.
The study will treat 66 patients at 2 clinical sites: UC Davis Center for Voice and Swallowing and UCSF Voice and Swallowing Center. Patients will be randomized 1:1 to receive either 2 AMDC-GIR doses of 150 x 10⁶ cells or 2 doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Enrollment is expected to be completed within 2 years of initiating the study. Patients will be followed for 24 months post-treatment.
Male and female patients at least 18 years of age who have undergone surgery and/or chemo- and/or radiotherapy for primary treatment of oropharyngeal squamous cell cancer and who present with symptoms and findings of TD will be eligible for participation. Eligible patients will have muscle tissue harvested using an established needle biopsy technique during an outpatient procedure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients will receive two treatments of intramuscular injection of 1 AMDC-GIR dose of 150 x 10⁶ cells or identical placebo. Both patients and study investigators at all sites will be blinded to the treatment assignment of patients.
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
- •Male or Female, at least 18 years old, with primary symptoms of TD following surgery and/or chemo- and/or radiotherapy for treatment of squamous cell carcinoma for oropharyngeal cancer. Treatment must be completed at least 24 months prior to enrollment, with TD and disease-free status confirmed by medical history, clinical symptoms, a focused head and neck examination, swallowing fluoroscopy, and high-resolution pharyngeal manometry.
- •TD severity should be moderate as defined by a Functional Oral Intake Scale (FOIS, provided in Appendix C). Individuals must have a FOIS of 3 or better and EAT-10 score of greater than
- •Patient has failed to achieve resolution of symptoms following contemporary therapies.
排除标准
- •Simultaneously participating in another investigational drug or device study or has completed the follow-up phase for the primary endpoint of any previous study less than 30 days prior to the first evaluation in this study.
- •Previously treated with an investigational device, drug, or procedure for TD within 6 months prior to signing consent.
- •TD of neurogenic etiology or uncorrected congenital abnormality leading to TD.
- •Neuromuscular disorder (e.g., Parkinson's disease, muscular dystrophy, multiple sclerosis) that could lead to TD.
- •Severe fibrosis at injection site.
- •Uncontrolled diabetes.
- •Compromised immune system due to disease state, chronic corticosteroid use, or other immunosuppressive therapy.
- •Medical condition or disorder that may limit life expectancy or that may cause CIP deviations (e.g., unable to perform self-evaluations or accurately report medical history, symptoms, or data).
- •History of bleeding diathesis or uncorrectable coagulopathy.
- •Known allergy or hypersensitivity to bovine proteins or allergens, gentamicin sulfate, or ampicillin that medically warrants exclusion as determined by the physician.
- •Any non-skin cancer that has necessitated treatment within the past 24 months.
- •Patient's Current Status-based Criteria:
- •Evidence or known high risk of recurrent or persistent cancer as determined by the physician during screening.
- •Tests positive for Hepatitis B (required tests: Hepatitis B Surface Antigen [HBsAg] and Anti-Hepatitis B Core Antibody [Anti-HBc]), Hepatitis C (required test: Hepatitis C Antibody [Anti-HCV]), HIV (required tests: HIV Type 1 and 2 Antibodies [Anti-HIV-1, 2]), and/or Syphilis.
- •a. Tests performed by certified/authorized testing laboratory using licensed/approved tests and performed on blood samples collected within 30 days prior to muscle tissue procurement.
- •Cannot, or is not willing to maintain the current treatment regimen for existing contemporary therapy (e.g., swallowing therapy).
- •Requires prophylactic antibiotics for chronic infection or has required 2 or more courses of antibiotics for infections in the 2 months prior to signing consent.
- •Any condition, including current infection or immunodeficiency, which could lead to significant postoperative complications.
- •Refuses or cannot provide written informed consent.
- •Not available for, or willing to comply with the baseline and follow-up evaluations as required by the CIP.
- •Pregnant, lactating, or plans to become pregnant during the course of the study.
研究组 & 干预措施
Experimental: 150 x 10⁶ AMDC-GIR dosage
33 subjects will be receiving two doses of 150 x 10⁶ AMDC-GIR spaced 4-6 weeks apart.
干预措施: Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) (Biological)
Experimental: Identical Placebo composed of the same cryopreservation medium used for AMDC-GIR
33 subjects will be receiving two doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Doses will be spaced 4-6 weeks apart.
干预措施: Placebo (Other)
结局指标
主要结局
Study product-related, biopsy procedure-related, and injection procedure-related adverse events.
时间窗: 24 months
Safety will be determined by the frequency and severity of adverse events related to study procedures and study product.
Anterior tongue pressure measured from Iowa Oral Performance Instrument (IOPI)
时间窗: 24 months
Efficacy of AMDC-GIR in the improvement of objective Anterior Tongue Pressure Measurement (IOPI)
次要结局
- Incidence of patient aspiration pneumonia(24 months)
- Patient-reported dysphagia symptoms based on Eating Assessment Tool EAT10 score(24 months)
- Penetration Aspiration scale rating following swallowing fluoroscopy(24 months)
- Peak Pharyngeal pressure measurement from high-resolution manometry(24 months)
- Incidence of patient survival(24 months)