A Prospective Dose Finding Study of Iscador Infusion: Phase Ib Study With Prolonged Observation (ISINFULA)
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities
研究概览
简要总结
Prospective, dose-escalating mono-center open label dose-finding study without control group (3+3 design), including a follow-up on-treatment observation. In this study will be recruited 15 patients with a histologically or cytologically confirmed diagnosis of an advanced malignant disease during a therapy-free interval.Investigational drug:Iscador®P: fermented aqueous extract of mistletoe grown on pine tree (Viscum album L. subspecies austriacum (Wiesb.) Vollmann), licensed for subcutaneous (SC) application in Switzerland, Germany, Austria, Sweden, and South Korea in dosages up to 20 mg.
The initial dose group of the study is set to 40 mg Iscador®P.
详细描述
This is a prospective open label dose finding study (phase I) of Iscador®P in patients with histological or cytological confirmed diagnosis of an advanced malignant disease during a therapy-free interval. Primary objective : To determine the maximum tolerated dose (MTD) of Iscador®P as intravenous infusion in the aforementioned patient population, based on the incidence of dose-limiting toxicities (DLTs). Secondary objective :To investigate safety and tolerability of long-term intravenous infusion of Iscador®P based on incidence and severity of adverse drug reactions.
All patients are receiving best supportive care and may receive, if necessary, specified concomitant therapies, which should not interfere with the safety parameters chosen for this study.
Investigational therapy will be administered in six Dose Groups (DG): 10 mg, 20 mg, 40 mg, 90 mg, 140 mg and 200 mg Iscador®P. The initial dose group of the study is set to 40 mg Iscador®P.
The two lower dose groups (20 or 10 mg) will only be used in case of intolerance at 40 mg Iscador®P. Once per week patients receive intravenous infusions of Iscador®P dissolved in 250 ml of sodium chloride solution (0.9 %). After the 4-week period of the MTD estimation phase each subject will immediately be included into a follow up observation in which he/she receives the last well tolerated dosage they had or the next lower dosage than the currently investigated DG in the running phase Ib study depending on the current estimate of the MTD at that time.
Study entry of individual patients will be set apart by one week. Dosages of subsequent dose groups depend on the incidence of DLTs in former groups.
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
- •Voluntarily given written informed consent.
- •≥18 years of age.
- •Metastatic or locally advanced solid tumor, histologically or cytologically confirmed, no standard therapy available or standard therapy has failed.
- •Adequate organ function
- •Life expectancy ≥ 3 months, ECOG ≤
- •No ongoing or preceding therapy with mistletoe products.
- •Women of childbearing potential: negative serum pregnancy test at screening, use of two adequate barrier methods
- •Compliance with protocol, legal competence.
排除标准
- •- Systemic cytotoxic chemotherapy, biological therapy, radiation therapy, OR major surgery prior trial treatment.
- •Persisting toxicity of NCI-CTCAE Grade >1 related to prior therapy (Sensory neuropathy of Grade ≤2 is acceptable).
- •Expected to require any other form of systemic or localized antineoplastic therapy while on trial
- •Systemic corticosteroid therapy received ≤ 3 days prior to trial treatment or other forms of systemic immunosuppressive medication (except corticosteroids against immune-related AEs and /or premedication for IV contrast allergies/reactions; corticosteroid replacement therapy)
- •Tumor and/or metastases of the CNS and/or carcinomatous meningitis
- •Active infection requiring intravenous systemic therapy, HIV, severe allergic illness (including asthma), active tuberculosis, inflammatory diseases with body temperature > 38° C.
- •Known hypersensitivity to mistletoe products.
研究组 & 干预措施
Iscador®P as intravenous infusion
Investigational therapy will be administered in six Dose Groups (DG):
10 mg, 20 mg, 40 mg, 90 mg, 140 mg and 200 mg Iscador®P. The initial dose group of the study is set to 40 mg Iscador®P. The two lower dose groups (20 or 10 mg) will only be used in case of intolerance at 40 mg Iscador®P. Once per week patients receive intravenous infusions of Iscador®P dissolved in 250 ml of sodium chloride solution (0.9 %). After the 4-week period of the MTD estimation phase each subject will immediately be included into a follow up observation in which he/she receives the last well tolerated dosage they had or the next lower dosage than the currently investigated DG in the running phase Ib study depending on the current estimate of the MTD at that time.
干预措施: Intravenous Solution (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities
时间窗: Subjects will be in this study for up to 58 weeks ( 4 weeks of treatment and follow-up for a maximum of 52 weeks if subjects are deemed to have continuous clinical benefit from the Iscador®P infusions.
Maximum tolerated dose (MTD) of Iscador®P infusions, i.e. the dose eliciting dose-limiting toxicities (DLTs) in a maximum of 1 out of 6 patients treated at that dose.treated at that dose.
次要结局
- Overall survival(4 weeks and follow up period for a maximum of 52 weeks)
- Quality of Life as Assessed Using Functional Assessment of Cancer Therapy - General (FACIT-G)(Baseline and prior to each infusion in phase I and monthly in the follow-up period.4 weeks and follow up period for a maximum of 52 weeks)
- Tumor response(4 weeks and follow up period for a maximum of 52 weeks)
- Incidence of adverse drug reactions (ADRs).(Subjects will be in this study for up to 58 weeks ( 4 weeks of treatment and follow-up for a maximum of 52 weeks if subjects are deemed to have continuous clinical benefit from the Iscador®P infusions.)
- Progression-free survival(4 weeks and follow up period for a maximum of 52 weeks)