Open Label Phase I Clinical Trial of Crotoxin in Patients With Advanced Cancer Using an Intravenous Route of Administration
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Tolerability of intra-patient dose escalation
研究概览
简要总结
The primary objective of the study is to assess whether human subjects can be made tolerant to intravenously administered Crotoxin and achieve higher and more therapeutically effective doses levels without the previously reported adverse effects associated with bolus i.m. administration.
详细描述
Crotoxin has been shown to induce neurotoxic tolerance in animals allowing them to receive high doses associated with effective anti-tumor activity in the absence of adverse side effects.
The study plans to demonstrate this effect in human subjects using two dose escalation protocols; slow and fast. It is believed that this approach will prevent toxic side effects to subjects.
The route of administration has not been employed clinically and is designed to avoid the myonecrotic effects of intramuscular injections. The target maximum dose is almost five times that of the previously reported MTD.
The revised protocol incorporates continuous infusion with a mobile pump and includes active suppression of the allergic reaction by pre-treatment administration of antihistamines.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will:
- •Be adult patients with histologically confirmed advanced solid tumors (excluding basal cell, colon, pancreatic and stomach cancers) who have progressed despite standard therapy, or for whom no standard therapy exists.
- •Have an ambulatory PS (ECOG 0-1).
- •Have tumor evaluation made within 28 days before study drug administration
- •Have completed radiotherapy or chemotherapy or any other anticancer therapy (including experimental therapy) more than 4 weeks prior to enrolment into the trial and must have recovered from all acute side effects of these treatments
- •Have a life expectancy greater than 3 months
- •Have an age ≥ 18 years
- •Have normal marrow function with the following haematological parameters normal; Hb ≥10g/dl, WBC ≥4.0 x10E9/L, neutrophil count ≥ 2.0 x 10E9/L and platelets ≥100 x10E9 /L
- •Have no medically significant impairment of cardiac or respiratory functions<
- •Have adequate hepatic function with Total bilirubin 1.5 x N and Transaminases < 2.5 x N (< 5 x N in case of liver metastasis).
- •Have no history of prior severe allergic reactions to venoms
- •Have Creatinine clearance > 50 mL/min.
- •Be on stable doses of any drugs which may affect hepatic drug metabolism or renal drug excretion (e.g.--non-steroidal anti-inflammatory drugs, barbiturates, narcotic analgesics, probenecid). Such drugs should not be initiated while the patient is participating in this study.
- •Not be pregnant or planning to become pregnant
- •Not known to have brain metastases or leptomeningeal involvement. CT-scan or MRI is not required to rule this out unless there is clinical suspicion of central nervous system involvement
- •Not have pleural effusion/ ascites, cystic lesions or bone metastases, as the only assessable lesions
- •Not have a history of other malignancies, except for patients with a cancer free interval of > 5 years after treatment completion, patients with prior history of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
- •Not have had recent major surgery (within 21 days).
- •Not have a recent history of weight loss > 10% of current body weight.
- •Not have serious intermittent medical illnesses which would interfere with the ability of the patient to carry out the treatment program.
- •Not be on chronic steroid medication (> 20mg/day)
- •Not have primary or paraneoplastic myasthenia gravis
- •Be free of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
- •Will agree to participate in the study prior to starting with any specific study procedure, after having signed written informed consent.
- •Be patients of childbearing age willing to use contraceptive for the duration of the study
- •Not live alone and live no further than approximately 30 km away from the hospital, and for the study duration have continuous access to the use of mobile telephone in case of medical emergency
排除标准
- 未提供
研究组 & 干预措施
Cohort 3
The third cohort will include up to 24 patients with Crotoxin doses of 0.2 to 1.32 mg per m2 in which the dose escalation speed will be faster. Drug is administered over 3 + 4 day intervals using ambulatory infusion pumps; treating on an outpatient basis. Subjects will receive increasing doses over the course of 28 treatment days (8 dose levels). Dose escalation will continue if DLT is not established
干预措施: Crotoxin (Drug)
结局指标
主要结局
Tolerability of intra-patient dose escalation
时间窗: 28 days
Assess the safety and tolerability of Crotoxin administered intravenously to Stage IV cancer patients using intra-patient dose escalation procedure.
Confirmation of the induction of drug tolerance
时间窗: 28 days
Confirm in a controlled phase I trial that human subjects can be made tolerant to intravenously administered Crotoxin thereby reducing the potential for adverse drug effects
次要结局
- Assessment of drug efficacy(112 days)