A Phase I, Exploratory, Intra-patient Dose Escalation Study to Investigate the Preliminary Safety, Pharmacokinetics, and Anti-tumor Activity of Pasireotide (SOM230) s.c.Followed by Pasireotide LAR in Patients With Metastaticmelanoma or Metastatic Merkel Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of patients with laboratory abnormalities and changes in laboratory values
研究概览
简要总结
This study will evaluate the preliminary safety, pharmacokinetics, and anti-tumor activity of pasireotide s.c. in patients with metastatic melanoma or metastatic Merkel cell carcinoma. The study consists of three phases: screening, intra-patient dose-escalation, and follow-up phases.
In the screening phase patient will be informed of all aspects of the study and sign informed consent forms and then be screened for study eligibility.
During the intra-patient dose escalation phase, 18 patients will be treated with pasireotide s.c. 300 μg t.i.d. for 2 weeks. If there are no unacceptable AEs, defined as drug-related clinically meaningful, uncontrolled grade 3 or any grade 4 toxicities, patients will be dose escalated to 600 μg t.i.d. for 2 more weeks, then 900 μg t.i.d. for 2 weeks and then 1200 μg for 2 weeks provided that there are no unacceptable AEs. Each patient will be in the dose escalation phase for a maximum of 8 weeks.
At end of the intra-patient dose escalation phase, patients will be allowed to switch to 80 mg pasireotide LAR i.m. q 28 d (or a lower dose in case of toxicity) for an additional 6 months or until disease progression, or unacceptable AEs, or patient withdraws consent. In addition, all patients will keep their pasireotide s.c. t.i.d. treatment (same dose as that at the end of the 8-week dose escalation phase) during the first 2 weeks of the LAR follow-up phase, except on the day receiving the first LAR dose because of an anticipated initial burst of drug release.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Pasireotide sub-cutaneous formulation
Pasireotide, will be administered to all patients by s.c. injection, beginning with a dose of 300 μg administered three times daily (t.i.d.) for 2 weeks. If no pasireotide-related clinically meaningful/uncontrolled grade 3 or grade 4 adverse events occur the dose will be administered to all patients at an increased dose of 600 μg t.i.d. for 2 weeks, followed by 2 weeks of 900 μg t.i.d. and followed by 2 weeks of 1200 μg t.i.d. After the 8 weeks period, patients will be kept on treatment drug (highest dose without clinically meaningful/uncontrolled AEs), switched to the corresponding pasireotide LAR dose and followed up for an extra 6 months.
干预措施: Pasireotide sub-cutaneous formulation (Drug)
Pasireotide long acting release
At the start of the follow-up phase patients will be switched to pasireotide LAR administered intramuscularly every 28 days by using the following conversion algorithm so that the steady state PK exposure (Cmax and Ctrough) of pasireotide will be maintained: 300 μg s.c. t.i.d. fi 20mg LAR i.m. q 28 days 600 μg s.c. t.i.d. fi 40 mg LAR i.m. q 28 days 900 μg s.c. t.i.d. fi 60 mg LAR i.m. q 28 days 1200 μg s.c. t.id. fi 80 mg LAR i.m. q 28 days In addition, all patients will keep the treatment with pasireotide s.c. during the first 2 weeks of the LAR phase. The use of s.c. dosing during the initial 2 week period following the first LAR dose provides an appropriate level of medication during the LAR nadir.
干预措施: Pasireotide lon acting release formulation (Drug)
结局指标
主要结局
Number of patients with laboratory abnormalities and changes in laboratory values
时间窗: Week 8
Number of patients with laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of patients with AEs, SAEs
时间窗: Week 8
Number of patients with AEs (overall and by severity) SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of patients with electrocardiographic abnormalities and changes in electrocardiograms readings
时间窗: Week 8
Number of patients with ECG according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of patients with vital sign abnormalities and changes in vital signs
时间窗: Week 8
Number of patients with vital sign abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
次要结局
- Tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) as measured by disease control rate ((DCR), (Complete Response (CR), Partial Response (PR), Stable Disease (SD))(Baseline, Day 57, Day 113, Day 169, Day 225)
- Changes from baseline on melanoma response biomarkers (MIA, S100B) overtime and its correlation with each dose(Baseline, Day 8, 15, 22, 29, 36, 43, 50, 57, 113, 169 and 225)
- Number of patients with vital sign abnormalities and changes in vital signs at study completion(Day 253)
- Changes from baseline and/or actual levels of potential response and/or secretion biomarkers over time, in repeated tumor and/or blood samples(Baseline, Day 1, 15, 29, 43, 57, 113, 169 and 225)
- Number of patients with AEs, SAEs at study completion(Day 253)
- Number of patients with electrocardiographic abnormalities and changes in electrocardiograms readings at study completion(Day 253)
- Number of patients with laboratory abnormalities and changes in laboratory values at study completion(Day 253)
- Changes in laboratory values, electrocardiograms readings, and vital signs values at study completion(Baseline, Day 253)
- PK parameters for each cycle on Day 1 (Cmax,d1 Tmax,d1, AUC0-2hr,d1), and on day 8 at steady state (Cmin,d8, Cmaxd8, Tmax,d8, Cavg,d8, AUC0-2hr,d8, ARd8)(Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 85, 113, 141, 169, 197 and 225)