NCT01445522已完成1 期
A Phase I Study of ABT-888 in Combination With Metronomic Cyclophosphamide in Adults With Refractory Solid Tumors and Lymphomas
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 4
- 主要终点
- Establish the safety and tolerability of the combination of ABT-888 with metronomic cyclophosphamide in patients with refractory solid tumors and lymphomas. Establish the MTD of the combination of ABT-888 with metronomic cyclophosphamide.
研究概览
简要总结
Background:
- Cyclophosphamide (CP) is a drug approved by the Food and Drug Administration for the treatment of certain cancers. It works by causing DNA damage, resulting in cell death, including cancer cells.
- ABT-888 is an experimental drug that has been given to a small number of patients. It works by preventing DNA repair in tumor cells.
Objectives:
- To test the safety of the combination of ABT-888 and CP, and to determine the dose of each drug that can be given together to patients with cancer.
- To see how the body handles ABT-888 when given together with CP
- To evaluate the anti-tumor response of the drug combination.
Eligibility:
- Adults with solid tumors or lymphoid cancers (lymphoma and chronic lymphocytic leukemia) whose disease does not respond to standard treatments.
Design:
- Patients take ABT-888 by mouth once a day for 7, 14 or 21 days, depending on the dose level assigned to the individual patient.
- Patients take CP by mouth once a day every day in 21-day cycles. (Some patients take CP for 14 days only.)
- Patients undergo tests and procedures periodically during the study, including:
- Clinic visit and physical examination at the beginning of each cycle
- Blood and urine tests, electrocardiogram, measurement of vital signs
- CT scans, MRI scans or ultrasound tests to check the response of the tumor to treatment
- Tumor biopsies (optional)
- Bone marrow aspiration and biopsy
详细描述
Background:
- The poly (ADP-ribose) polymerase (PARP) family of enzymes is characterized by the ability to poly-ADP-ribosylate protein substrates. PARP-1 and PARP-2 play a critical role in the maintenance of genomic stability by regulating a variety of DNA repair mechanisms.
- PARP activity has been shown to be important in base excision repair pathways. The inhibition of PARP could inhibit the repair of the DNA damage caused by alkylating agents such as cyclophosphamide. ABT-888 has been shown to potentiate the action of cyclophosphamide in xenografts models. ABT-888 is an orally delivered PARP inhibitor and cyclophosphamide can be delivered orally as an alkylating agent.
- Metronomic therapy with cyclophosphamide has demonstrated efficacy in multiple tumor types including, but not limited to, ovarian cancer, lymphoma, prostate cancer, and breast cancer. Its activity has been at least partially attributed to mediation of anti-angiogenic effects through induction of apoptosis in endothelial cells.
Objectives:
- Establish the safety and tolerability of the combination of ABT-888 with metronomic cyclophosphamide in patients with refractory solid tumors and lymphomas.
- Establish the maximum tolerated dose (MTD) of the combination of ABT-888 with metronomic cyclophosphamide.
- Evaluate the pharmacokinetics of ABT-888 when administered combination with cyclophosphamide.
- Evaluate for anti-tumor response.
- Determine the effects of the study treatment on the level of PARP inhibition and gamma-H2AX in PBMCs and tumor samples.
Eligibility:
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 110 Years（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
结局指标
主要结局
Establish the safety and tolerability of the combination of ABT-888 with metronomic cyclophosphamide in patients with refractory solid tumors and lymphomas. Establish the MTD of the combination of ABT-888 with metronomic cyclophosphamide.
次要结局
- Evaluate the pharmacokinetics of ABT-888 when administered combination with cyclophosphamide. Evaluate for anti-tumor response.
研究者
研究点 (4)
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