Fázis II, randomizált, kettős Vak vizsgálat a bőr metasztázisok kezelésére kálcium elektroporációval
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 7
- 主要终点
- Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
研究概览
简要总结
Electroporation is a method that can facilitate transport of molecules across the cell membrane and into the cell by means of electrical pulses. The method can be used with molecules that normally have difficulty passing the cell membrane such as chemotherapy (electrochemotherapy). Electrochemotherapy (ECT) is used in cancer therapy, where chemotherapy is administered intratumoral or intravenous, then followed by electrical pulses applied directly on the tumor. The chemotherapy accumulates in the cancer cells which results in an increased cytotoxic effect. The most used chemotherapeutic drug used in electrochemotherapy is bleomycin. Electrochemotherapy is a well-documented local treatment form for especially cutaneous tumors. Today, the treatment is used mostly in palliative care in more than 140 centres around Europe.
In vitro and in vivo studies have shown that the combination of calcium and electroporation is an effective method in killing cancer cells without serious side effects.This new combination opens the possibility of replacing bleomycin with calcium in treatments with electroporation.
Calcium electroporation is a local treatment where calcium is administered intratumoral and followed by electrical pulses applied on the tumor.
The preclinical studies have shown that there is a difference in sensitivity in tumor cells and normal cells, as normal cells tolerate the treatment better than tumor cells (own data manuscript in preparation). The studies have also shown that there is no cell injury by calcium injection without electroporation, the investigators therefore expect that the treatment only will cause minor side effects.
Calcium electroporation would be possible to use on patients for whom chemotherapy is contradicted e.g. severe lung functions impairment, pregnant woman etc. Calcium electroporation is a simple and unexpensive cancer treatment that does not involve any administration of cytotoxic chemotherapy, and can be performed by surgeons, radiologists as well as oncologists. Both electroporation equipment and calcium are already being used in the clinic, so the treatment can easily be implemented.
详细描述
Trial Design for Treatment of Cutaneous Metastases:
The current study is a randomized double blinded phase II study comparing the effect of calcium electroporation with ECT with bleomycin on patients with cutaneous metastases of any histology. As calcium and bleomycin are administered intratumoral, only small metastases from 0.5-3 cm will be treated. The treatments will be compared in tumor response and adverse events. Treatment will be done in a palliative purpose.
Cancer patients with cutaneous involvement have often several metastases. A maximum of ten metastases will be included per patient. One to six metastases (depending on the patient's number of metastases) will be numbered 1-6 and randomized into one of two treatment arms
- Intratumoral calcium followed by electroporation
- Intratumoral bleomycin followed by electroporation Randomization will be performed separately on each metastasis, so the patient may receive both treatments. Calcium and bleomycin will be mixed into syringes labeled with numbers according to the metastases and both treating doctor and patient will be blinded to the content of the syringes.
If the patient has more than six metastases, then one to four metastases will be used for biopsy. The treatment of these metastases will be known, and biopsies will be performed before and after treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years.
- •Verified cutaneous metastases of any histology.
- •At least one cutaneous metastases between 0.5 to 3 cm and accessible to electroporation.
- •The patient should have been offered current standard treatment. If there is no further standard treatment to offer, or if the patient does not want to receive this, the patient may be included in the trial.
- •Treatment free interval of more than two weeks. However, patients treated with Navelbine (Vinorelbine) Capecitabine (Xeloda) or weekly paclitaxel (Taxol) can continue these treatments, if there is no regression of cutaneous metastases. Other medical cancer treatments such as endocrine treatment, targeted treatment and radiotherapy to another area may also continue.
- •Performance status World Health Organization (WHO) ≤
- •Expected survival of > 3 months.
- •Platelets ≥ 50 billion/L, international normalized ratio (INR) < 1.
- •Medical correction is allowed, e.g. correction of a high INR using vitamin K.
- •Sexually active men and women who can become pregnant should use adequate contraception during this trial (pill, spiral, injection of prolonged progestin, subdermal implantation, hormone-containing vaginal devices, transdermal patches).
- •The patient should be able to understand the information.
- •Signed informed consent.
排除标准
- •Previous bleomycin treatment with more than 200,000 U/m² .
- •History of severe allergic reactions associated with bleomycin.
- •Coagulation disorder which cannot be corrected.
- •Pregnancy and lactation.
- •Participating in other clinical trials involving experimental drugs or involved in a trial within 4 weeks prior to study drug administration.
结局指标
主要结局
Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
时间窗: 180 days after treatment
Documentation was done with digital color photography, including a ruler to estimate tumor size. Primary evaluation of the response was based on criteria similar RECIST 1.1 guidelines and defined as complete response (CR) - disappearance of the lesion, partial response (PR) - at least 30% decrease in the largest diameter of the lesion, progressive disease - at least 20% increase in the largest diameter of the lesion and stable disease - neither 30% decrease nor 20% increase of the largest diameter of the lesion. Change in the largest diameter:
次要结局
- Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).(180 days after treatment)
研究者
Erika Kis
Principal Investigator, Assistant Professor
Szeged University