A Phase 1 Multicenter, Open-label, Dose-escalation Trial of MBC-11, an Etidronate-ara-C Conjugate in Patients With Malignant Tumors With Cancer-induced Bone Disease (CIBD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
This study evaluates MBC-11 (a conjugate of a bone-targeting vehicle (etidronate) and a cytostatic agent [ara-C] in patients with malignant tumors with CIBD. This is a first use in human.
详细描述
A standard "3+3" dose escalation design to determine Maximum Tolerated Dose with consecutive different dose level cohort recruitment.
The following dose levels to be investigated: 0.5 mg/kg, 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, 10 mg/kgm 20 mg/kg. The study for each patient consists of 14-days screening period, single dose administration of MBC-11 followed by 7-day safety monitoring and then 2 cycles of multiple use of MBC-11 (28 days each cycle, study drug is administered at Days1-5). In case of partial metabolic reaction/stable metabolic reaction therapy maybe prolonged up to 4 cycles (at investigator and sponsor consideration)
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
- •Histologically confirmed malignant tumor (breast cancer, prostate cancer etc)
- •Bone metastases, documented by radiographs, bone scan
- •No available standard chemotherapy or no indication for chemotherapy at the time of screening
- •Eastern Cooperative Oncology Group [ECOG] status 0-2
- •Adequate bone marrow function (hemoglobin ≥ 9 g/dL with or without transfusion requirement, absolute neutrophil count ≥ 1500/mm3, and platelets ≥ 75,000/mm3)
- •Adequate liver function (bilirubin ≤ 2 x Upper Limit of Normal [ULN], Alanine aminotransferase [ALT] ≤ 2.5 x ULN).
- •Adequate renal function (creatinine ≤ 1.5 x ULN) and creatinine clearance ≥ 50 mL/min [measured or calculated by nomogram]).
排除标准
- •Systemic chemotherapy and/or investigational therapy within the previous 4 weeks
- •Fracture ≤ 6 month prior the inclusion in the study
- •Brain metastasis
- •Serum calcium levels < 8.5 mg/dL (< 2.2 mmol/L)
研究组 & 干预措施
dose escalation of MBC-11
MBC-11 was administered in 5 consecutively recruited cohort in dose 0.5 mg/kg, 1 mg/kg, 2.5 mg/kg, 5 mg/kg,10 mg/kg accordingly. The dose escalation is aimed at determining the maximum tolerated dose (MTD)
干预措施: MBC-11 (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: up to 20 weeks
Incidence of Treatment-Emergent Adverse Events
时间窗: up to 20 weeks
evaluation of adverse events, physical examination, laboratory parameters
Dose Limiting Toxicity [DLT]
时间窗: up to 20 weeks
dose limiting toxicity is graded according to NCI CN CFT version 4
次要结局
- Maximum Plasma Concentration [Cmax] of ara-U(5 weeks)
- Peak time [Tmax] for MBC-11(5 weeks)
- Peak time [Tmax] for etidronate(5 weeks)
- Maximum Plasma Concentration [Cmax] of MBC-11(5 weeks)
- Maximum Plasma Concentration [Cmax] of etidronate(5 weeks)
- Pharmacodynamic parameters(up to 20 weeks)
- Fluorodeoxyglucose positron emission tomography-computed tomography [FDG PET-CT] response after cycle 2 and cycle 4 therapy(up to 20 weeks)