A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 86
- 试验地点
- 7
- 主要终点
- Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
研究概览
简要总结
This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the proteasome inhibitor NPI-0052 in patients with advanced malignancies including solid tumors, lymphomas, leukemias and multiple myeloma. By inhibiting proteasomes NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and survival in cancer cells.
详细描述
Patients were enrolled in 1 of 2 study arms. Arm AM (weekly doses of NPI-0052) consisted of patients with solid and hematological malignancies excluding multiple myeloma (MM), and these patients received NPI-0051 once weekly for 3 weeks of every 4 weeks. Arm MM (twice-weekly doses of NPI-0052) consisted of patients with MM and other hematological malignancies, and these patients received NPI-0052 twice weekly for 2 weeks of every 3 weeks. All patients received NPI-0052 administered IV over approximately 1 to 120 minutes. Patients with MM (Arm MM) also received 20 mg dexamethasone per orally or IV on the day before and the day of NPI-0052 dosing.
Patients were initially enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of NPI-0052. Once the RP2D was determined for each arm of the study, the RP2D was evaluated in the dose-expansion stage of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Karnofsky Performance Status (KPS) > 70%.
- •Histologically-confirmed advanced malignancy for which a standard, approved therapy is not available.
- •Adequate renal, liver, pancreatic and hematologic function
- •Signed informed consent (sample IC form is provided in Appendix A).
- •Exclusion Criteria
- •Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days
- •Patients that require G-CSF and/or platelet support during screening and are likely to require G-CSF and/or platelet support for the duration of the clinical trial.
- •Patients with ongoing coagulopathies and/or taking anticoagulants
- •Patients receiving intrathecal therapy.
- •Known brain metastases.
- •Pre-existing adrenal insufficiency; concomitant therapy with replacement corticosteroids. Pre-existing acute or chronic pancreatitis.
- •Significant cardiac disease.
- •Pregnant or breast-feeding women.
- •Concurrent, active secondary malignancy for which the patient is receiving therapy. (Lymphoma patients with a diagnosis of a potentially hormone-sensitive tumor who are without evidence of disease for this second malignancy may continue to receive hormonal therapy).
- •Patients with proteinuria Grade 2 or greater
- •Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics.
- •Patients who are known to be HIV positive or have active Hepatitis A, B, or C infection.
排除标准
- 未提供
研究组 & 干预措施
Arm AM: advanced malignancies
Dose Escalation - 9 dose cohorts NPI-0052 on Days 1, 8, 15 every 28 days NPI-0052 doses ranging from 0.1 to 0.9 mg/m2
干预措施: NPI-0052 on Days 1, 8, 15 every 28 days (Drug)
Arm MM: multiple myeloma
Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.
干预措施: NPI-0052 on Days 1, 4, 8, 11 every 21 days (Drug)
Arm MM: multiple myeloma
Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
时间窗: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Assess dose-limiting toxicities during Cycle 1 for each treatment arm
次要结局
- To evaluate the pharmacokinetics activity of NPI-0052(Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1)
- To evaluate the safety and tolerability of NPI-0052(Treatment period through 28-days after the last dose of study drug)
- To evaluate the pharmacodynamics of NPI-0052(Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycles 1 and 2 and of every other cycle thereafter through study completion)