Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Histopathologic tumor regression following electrochemotherapy
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE).
详细描述
Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumor cells more porous which allows the drug easier access into the cancer cells, whereas other tissues and organs in the body remain relatively poor at absorbing the drug, thereby reducing the potential side effects on healthy tissues. Procedures with electrochemotherapy have previously been applied to human patients in other countries of the EU, the US and Japan.
The drug concentration used is significantly reduced due to the more targeted absorption by the tumor and this significantly reduces side effects normally associated with chemotherapy.
A large number of preclinical and clinical Phase I and I/II studies have demonstrated the efficiency and safety of ECT. These studies have included patients with melanoma, head and neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma nodules.
An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors has recently been developed. The treatment procedure is similar to standard endoscopic colorectal examination (therapeutic colonoscopy) with the added element of an intravenous injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire procedure is minimally invasive and completely ambulatory. A successful treatment will cause the tumor to shrink in size in the weeks following the procedure.
The objective of this study is to investigate the efficacy and safety of this approach in downsizing locally advanced rectal tumors prior to intended curative surgery.
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
- Single (Outcomes Assessor)
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
- •Patient must be mentally capable of understanding the information given.
- •Patients must give written informed consent.
- •Men or women aged at least 18 years.
- •Histologically verified rectal tumor (adenocarcinoma)
- •Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with neoadjuvant therapy followed by surgical excision (UICC stadium II-III).
- •ASA class I-III (Classification of the American Society of Anesthesiology)
排除标准
- •Coagulation disorders
- •Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
- •Patients with ICD or pacemaker units.
- •Patients with epilepsy.
- •Pregnancy or lactation/breastfeeding.
- •Patients with known Hepatitis B/C or HIV infection.
- •Patients who have undergone treatment with bevacizumab within 4 weeks prior to enrolment in this trial.
- •Patients with concomitant use of phenytoin.
- •Patients with concomitant use of clozapine.
- •Concurrent treatment with an investigational medicinal product.
- •Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study recruitments.
- •Patients with contraindications for PET/MRI scan:
- •Advanced tumor stage, UICC stage IV.
- •Acute pulmonary infection.
- •Medical history of severe pulmonary disease.
- •Previous allergic reactions to bleomycin.
- •Previous cumulative dose of bleomycin exceeding 250.000 IU/m
- •Pre-existing renal dysfunction. Creatinine clearance < 40 ml/min.
- •Platelet count ≤50 mia/l.
- •Prothrombin time ≥ 40 sec
- •Patients registered in the Danish Tissue Register (Vaevsanvendelsesregistret)
研究组 & 干预措施
Electrochemotherapy with bleomycin
Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.
BSA by Du Bois formula.
干预措施: Electrochemotherapy with bleomycin (Drug)
Electrochemotherapy with bleomycin
Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.
BSA by Du Bois formula.
干预措施: EndoVE (Device)
结局指标
主要结局
Histopathologic tumor regression following electrochemotherapy
时间窗: 4 weeks
Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)
次要结局
- Treatment safety of electrochemotherapy(4 months)
- Treatment safety of surgery following electrochemotherapy(4 weeks)
- Tumor regression according to Hybrid PET/MRI following electrochemotherapy(4 weeks)
- Tumor Immunologic response following electrochemotherapy(4 weeks)