Pharmacokinetic, Pharmacodynamic and Interleukin Profile of Intramuscularly Administered BP-C1 in Women With Metastatic Breast Cancer. A Phase ID Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Meabco A/S
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Single-dose PK: Maximum Observed Serum Concentration (Cmax) for Platinum
研究概览
简要总结
This study is an open label, non-randomized phase I single-armed study in women with metastatic breast cancer (MBC) who have previously undergone all available standard chemotherapy regimens. The purpose of the study is to estimate the pharmacokinetics (PK) after single dose and multiple dose of BP-C1, investigate interleukin levels during BP-C1 treatment and assess treatment response according to RECIST criteria.
详细描述
BP-C1, solution for injections 0.05%, is currently being developed for treatment of patients with metastatic breast cancer with palliative intent.
Active substance of the product, which is a novel platinum-containing anticancer agent developed for intramuscular administration, is а cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin.
The amphiphilic characteristics of the polymer have resulted in a product with clear and significantly altered and improved properties compared to other platinum analogues, e.g. cisplatin, carboplatin and oxaliplatin.
BP-C1 preserves antitumour activity of its predecessors (e.g. cisplatin and carboplatin), additionally offering the following advantages that ensure favourable outcome of treatment of metastatic breast cancer patients:
- injectable solution (intramuscular) does not cause injection site reactions;
- can be administered at home by a nurse or a patient;
- has an improved pharmacokinetic profile;
- demonstrates efficacy comparable to cisplatin and much higher than carboplatin (in-vitro; in-vivo data);
- exerts an additional immunomodulatory activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients with metastatic breast cancer (MBC, stage IV).
- •18 and 80 years of age.
- •Measurable lesions / lymph nodes.
- •Have previously undergone at least third line chemotherapy.
- •Expected survival time at least 3 months.
排除标准
- •Abnormal liver function classified as total bilirubin >34 μmol/L or ALAT > 3 times the upper limit of normal range (ULN). In case of metastases in the liver, the ALAT limit for exclusion is set to 5xULN. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
- •Abnormal kidney function defined by serum creatinine >120 μmol/L. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
- •Abnormal coagulation capacity defined by the relative arbitrary concentration of coagulation factors 2,7,10 INR >1.
- •Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
- •Brain metastases in symptomatic patients requiring ≥4 mg dexamethasone/day. However, patients with treated brain metastases by surgery or radiation who are stable and symptom-free (<4 mg dexamethasone/day) for a minimum period of 4 weeks prior to study treatment are eligible.
- •Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
- •Abnormal haematology status defined by Hb < 9.0 g/dL, platelet count < 75,000/mm^3 and leukocytes < 3x10^9/L. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
- •Clinically significant abnormal ECG.
- •Karnofsky Performance Status Score < 50%.
- •Pregnant or breast feeding women.
- •Women of fertile age who do not want to be tested for possible pregnancy.
- •Fertile female who do not want to use safe protection against pregnancy, starting one month before start of the trial treatment and lasting at least six weeks after.
- •Uncontrolled bacterial, viral, fungal or parasite infection.
- •Under systemic treatment with corticosteroids or other immunosuppressive drugs during the last 21 days before start of the trial treatment. Systemic treatment with <4 mg dexamethasone/day is allowed
- •Participating in another clinical trial with pharmaceuticals during the last six weeks before start of this trial treatment.
- •Not able to understand written or oral information.
- •Do not want or is not able to give written consent to participate in the study.
研究组 & 干预措施
BP-C1 IM Injections
BP-C1 given in daily intramuscular doses of 0.035 mg/kg bodyweight in one syringe per day during a total treatment of 32 days.
干预措施: BP-C1 (Drug)
结局指标
主要结局
Single-dose PK: Maximum Observed Serum Concentration (Cmax) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Maximum Observed Serum Concentration (Cmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Multiple-dose PK: Time to Reach Maximum Observed Serum Concentration at steady state (Tss,max) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Time for Css,max at steady state for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Area under the serum concentration versus time curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) during the period of Day 32 to Day 34
Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC(0-t)) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
AUC(0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Serum Decay Half-Life (T1/2) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose during the period of Day-1 to Day 1
Serum decay half-life is the time measured for the serum concentration of Platinum to decrease by one half after the single dose of BP-C1 during the period of Day-1 to Day 1
Multiple-dose PK: Maximum Observed Serum Concentration at Steady State (Css,max) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Maximum Observed Serum Concentration at steady state (Css,max) for Platinum during the period of Day 32 to Day 34
Single-dose PK: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC(0-∞))
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
after the single dose of BP-C1 during the period of Day-1 to Day 1
Multiple-dose PK: Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Average Serum concentration at steady state (Css,av) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Average Serum concentration at steady state (Css,av) for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Serum Decay Half-Life (T1/2) for Platinum
时间窗: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Serum decay half-life is the time measured for the plasma concentration of Platinum to decrease by one half during the period of Day 32 to Day 34
次要结局
- Interleukin Serum levels (Interferon γ and β, Tumour Necrosis Factor (TNF-α), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-21 and IL-25)(Day-1, Day 1, Day 16, Day 32, Day 34)
- Change (%) in the sum of diameters of target lesions(baseline to Day 32 of treatment)
- Number of target lesions(baseline to Day 32 of treatment)
- Treatment response(baseline to Day 32 of treatment)