A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide
研究概览
简要总结
Background:
- Pomalidomide is a drug that can treat cancer through several mechanisms. It is taken by mouth (orally). Pomalidomide can help treat cancer by blocking certain factors that promote tumor growth or by stimulating the immune system to attack tumor cells. It also prevents the growth of new blood vessels that help cancer grow. Researchers want to see if pomalidomide can treat Kaposi sarcoma, a rare and potentially fatal skin cancer. Because Kaposi sarcoma may be associated with human immunodeficiency virus (HIV) infection, researchers want to test the drug in people with and without HIV infection.
Objectives:
- To see if pomalidomide is a safe and effective treatment for Kaposi sarcoma in people with or without HIV.
Eligibility:
- Individuals at least 18 years of age who have Kaposi sarcoma.
- Participants may or may not have HIV infection.
Design:
- Potential participants will be screened with a medical history and physical exam. Blood and saliva samples will be taken and a chest X-ray will be performed. A skin biopsy of a Kaposi sarcoma lesion may be performed if one has not already been done. Other imaging studies may be performed if needed.
- Participants will take pomalidomide capsules every day for 3 weeks, followed by a 1-week break. These 28 days are one cycle of treatment.
- Participants will have up six cycles of treatment, unless the lesions completely resolve sooner. If there are signs of improvement after six cycles but the lesions are not completely gone, up to another six cycles of treatment may be given.
- Treatment will be monitored with frequent blood tests and other studies including photograph and other imaging of skin lesions.
- Participants will have regular follow-up visits for 5 years after stopping treatment....
详细描述
Background:
Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently involves the skin. It is seen most frequently in people with human immunodeficiency virus (HIV) or other forms of immune compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable long-term for relapsing disease are all lacking.
Objective:
The primary objective of this study is to:
Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
Phase 1 Pomalidomide 5mg Daily
Up to six subjects will initially be treated with for 21 days of a 28 day cycle
干预措施: Pomalidomide (Drug)
Phase 2 Pomalidomide 5mg Daily
15 human immunodeficiency virus (HIV) positive and 10 HIV negative subjects evaluable for response will be treated with Pomalidomide 5mg daily for 21 days of a 28 day cycle
干预措施: Pomalidomide (Drug)
结局指标
主要结局
Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide
时间窗: During each cycle and 4 weeks after completing therapy, with any continuing AE's observed until resolution, approximately 124 months and 1 day.
Adverse events (AE's) that are possibly, probably, and/or definitely attributed to pomalidomide were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening.
Time to Maximum Observed Serum Concentration of Pomalidomide (Cmax)
时间窗: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Time to maximum observed serum concentration of Pomalidomide was reported.
Half-Life of Pomalidomide
时间窗: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Maximal Plasma Concentration (Cmax) of Pomalidomide
时间窗: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Plasma concentrations of pomalidomide were assayed using high-performance liquid chromatography with fluorescence detection with a lower limit of quantitation of 1 ng/mL and were recorded as observed values. A non-compartmental analysis was used to calculate plasma pharmacokinetic parameters (Pharsight, Mountain View, California).
Area Under the Curve Extrapolated to Infinity (AUCinf)
时间窗: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
AUC is a measure of the serum concentration of Pomalidomide over time. It is used to characterize drug absorption. The AUC extrapolated to infinity was used, unless the percent extrapolated exceeded 25% in which case AUC to the last quantifiable time point (AUCLast) was used. The steady-state exposure on Day 15 of cycle 1 was calculated using AUCLast.
Progression Free Survival (PFS)
时间窗: time from day 1 of pomalidomide therapy until progression requiring a change in therapy, an average of 9.97 months
PFS is defined as time from day 1 of pomalidomide therapy until progression requiring a change in therapy, estimated using the Kaplan-Meier method. Progression was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions.
Area Under the Plasma Concentration Versus Time Curve (AUC) to the Last Timepoint (AUCLast)
时间窗: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
Area under the plasma concentration versus time curve (AUC) was calculated using the log-linear trapezoidal method. The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
次要结局
- Antitumor Effect of a Second Course of Pomalidomide(After completion of 2 cycles of therapy up to 48 weeks after the start of the second course of Pomalidomide)
- Percentage of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions(Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy)
- Antitumor Effect of a First Course of Pomalidomide(After completion of 2 cycles of therapy up to 48 weeks)
- Change in Cytokines From Baseline to 4 Weeks, Baseline to 8 Weeks and End of Treatment(Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment)
- Change in Immune Cytokines Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Cluster of Differentiation 19 (CD19) Among Participants With and/or Without Human Immunodeficiency Virus (HIV)(Baseline to 4 weeks, baseline to 8 weeks, and baseline to end of treatment)
- Change Between Timepoints Baseline to 4 Weeks, Baseline to 8 Weeks, and Baseline to End of Treatment in Kaposi Sarcoma-Associated Herpesvirus (KSHV) Viral Load(Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment)
- Human Immunodeficiency Virus (HIV) Viral Load(Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment)
- Self-Reported Health-Related Quality of Life (HRQL) Instrument: Functional Assessment of Human Immunodeficiency Virus Infection (FAHI)(Baseline, after 3 months of therapy, and after completion of therapy, up to 48 weeks)
- Number of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions(Baseline, timepoint 1: after 3 months of therapy, and timepoint 2: 1 month after completion of therapy)
研究者
Robert Yarchoan
Principal Investigator
National Cancer Institute (NCI)