Sodium Selenite as a Cytotoxic Agent in Advanced Carcinoma. A Phase I and Phase II Study.
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Maximal tolerable dose (phase I, ongoing)
研究概览
简要总结
In vitro studies have demonstrated that sodium selenite in sufficient concentration and during sufficient time have a high tumoricidal capacity. This is found in many human cell types as leukemia cells, mesothelioma and non-small cell lung cancer cells. A minority of cell lines seem to be resistant. The question from a clinical point of view is: Is it possible with respect to toxicity to administer sodium selenite to patients in sufficient dose and during sufficient time to get responses in patients with cancer? We have performed first part of phase-1 study and found MTD of 10.2 mg/m2 if given as 10 daily infusions during 12 days. We have recorded limited anti-tumor effect in this treatment regimen. However, in vitro data suggest that low concentration of continuous exposure for 51 h is much more effective. Now we are planning to continue the phase-I trial with modified protocol.
More specific:
- Phase I: Find maximal tolerable dose with continuous infusion
- Phase II: Use MTD and study responses, if any
详细描述
- Patients: With advanced malignant disease, any kind, in which all standard treatment has been tried, but still progression. In sufficient good performance status (ps 0-2)to get more treatment: first selenite and immediately afterwards chemotherapy (since an additive or synergistic effect from selenite and chemotherapy has been found).
- Treatment: We have performed the initial study with sodium selenite i.v. daily, 10 treatments during 2 weeks. The week after that response evaluation and then chemotherapy. In each patient, his or her first line chemotherapy treatment is given, since in vitro studies indicate that selenite might reverse resistance. In the modified protocol, a 2 days continuous infusion will be performed.
- Toxicity evaluation (main criteria in phase I): Meeting a doctor once a week during selenite treatment and before each chemotherapy treatment and at End of treatment. Meeting a nurse each treatment day during selenite treatment. Blood samples for liver, kidney, blood and thyroid values. Plasma samples for selenite concentration during treatment.
- Response evaluation (to be: main criteria in phase II and studied also in phase I): CT scan just before and after selenite treatment and after chemotherapy. From May 2011 FDG-PET-CT-scan just before and after selenite treatment. Cytokeratin and cytokeratin fragments evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Advanced malignant tumor disease
- •All standard treatments should have been tested, but the disease still progressing.
- •In sufficient good performance status to get more treatment
- •Informed consent
排除标准
- •More than 1 active tumour disease
- •Impaired capacity to cooperate
- •Serious other disease such as heart or kidney disease that might give extra risk for complications and difficulties to interpret effect of the selenite treatment
- •The tumour not possible to evaluate
研究组 & 干预措施
Selenite treatment
In the first part of the study, cohorts of 3 patients receive sodium selenite iv, starting with a dose of 0.5 mg/m2. If no serious adverse event the next cohort is treated according to a dose escalation schedule and this part has been completed. In the modified protocol, a continuous infusion over 2 days will be administered.
干预措施: Sodium selenite (Introselen) (Drug)
Selenite treatment
In the first part of the study, cohorts of 3 patients receive sodium selenite iv, starting with a dose of 0.5 mg/m2. If no serious adverse event the next cohort is treated according to a dose escalation schedule and this part has been completed. In the modified protocol, a continuous infusion over 2 days will be administered.
干预措施: Sodium selenite (Drug)
结局指标
主要结局
Maximal tolerable dose (phase I, ongoing)
时间窗: within three year
To find which kind and grade of toxicities that are dose-limiting
次要结局
- Responses(Two years within the phase I study)
研究者
Ola Brodin
MD, PhD, Ass Prof, Senior consultant
Karolinska University Hospital