A Multi-Arm Complete Phase 1 Trial of Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of valproic acid in combination with either dasatinib, erlotinib hydrochloride, lapatinib, lenalidomide, sorafenib, or SU011248 (sunitinib malate) that can be given to patients with advanced cancer. The safety of each combination of the study drugs will be studied as well.
详细描述
The Study Drugs:
Valproic acid is designed for use as an anti-seizure medication. It is thought to also have anticancer activity by activating ("turning on") tumor-fighting genes, which may cause cancer cell death.
Dasatinib is designed to change the function of genes. By changing the function of these genes, it may prevent cancer from growing and spreading.
Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
Lapatinib is designed to block the activity of certain molecules. These molecules play a part in the growth of cancer cells and are particularly important for the growth of inflammatory breast cancer tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have advanced solid tumor: they have either a disease where there is no established standard of care therapy or have failed one or more prior therapy. (for all treatment arms)
- •Patients must have ECOG performance status < or = 2 (0-2). Patients </=10 years modified Lansky scale >/=
- •Patients >10 to 18 years Karnovsky scale >/= 60.(for all treatment arms)
- •Patients must have normal organ and marrow function as defined below: Platelets > 50,000/uL; Creatinine clearance > 20mL/min (for all treatment arms); Total bilirubin < 5 mg/dL (except for Lapatinib arm); ALT </= 6X ULN for Lapatinib arm only;
- •(cont. from above) Liver function criteria and dosing based on each individual drug: Valproic acid - if ALT >/= 6X ULN or T. Bili >/= 3, then dose should be decreased by 50%; Sorafenib - If Child Pugh class A or B, no dose adjustment; if Child Pugh class C, decrease dose by 50% (400 mg po daily max); Sunitinib - If ALT >/= 6X ULN or T. Bili >/= 3 , decrease dose by 25% (37.5 mg po daily max);
- •(cont. from above) Erlotinib - If ALT > 6X ULN or T. Bili >/= 3 , decrease dose by 25% (100 mg po daily max); Lapatinib - If ALT > 3X ULN or T. Bili > 2X ULN, decrease dose by 60% (500-750 mg po daily max); Dasatinib - No dose adjustment needed; Lenalidomide - No dose adjustment needed.
- •Patients or legal representative must be able to understand and be willing to sign an IRB-approved written informed consent document. (for all treatment arms)
- •Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose. (for all treatment arms)
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, symptomatic cardiac arrhythmia, active bleeding, active thrombosis, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of allergic reactions to the study drugs or their analogs.
- •Failure to recover from any prior surgery within 4 weeks of study entry.
- •Any treatment specific for tumor control within 3 weeks of study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 4 half-lives for target agents with half lives and pharmacodynamic effects lasting less than 5 days (that include but are not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents); or failure to recover from the toxic effect of any therapy prior to study entry.
- •Study agents cannot be obtained for any reason since this study does not provide free agents.
- •Any prior history of hypertensive crisis or hypertensive encephalopathy.
- •Significant vascular disease (e.g., aortic aneurysm, aortic dissection) and symptomatic peripheral vascular disease
- •Evidence of bleeding diathesis or coagulopathy.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
- •Minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment; and serious, non-healing wound, ulcer, or bone fracture.
研究组 & 干预措施
VN
Valproic Acid + Sorafenib
干预措施: Sorafenib (Drug)
VN
Valproic Acid + Sorafenib
干预措施: Valproic Acid (Drug)
VS
Valproic Acid + Sunitinib
干预措施: Sunitinib (Drug)
VS
Valproic Acid + Sunitinib
干预措施: Valproic Acid (Drug)
VD
Valproic Acid + Dasatinib
干预措施: Dasatinib (Drug)
VD
Valproic Acid + Dasatinib
干预措施: Valproic Acid (Drug)
VT
Valproic Acid + Erlotinib
干预措施: Erlotinib (Drug)
VT
Valproic Acid + Erlotinib
干预措施: Valproic Acid (Drug)
VL
Valproic Acid + Lapatinib
干预措施: Lapatinib (Drug)
VL
Valproic Acid + Lapatinib
干预措施: Valproic Acid (Drug)
VR
Valproic Acid + Lenalidomide
干预措施: Lenalidomide (Drug)
VR
Valproic Acid + Lenalidomide
干预措施: Valproic Acid (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities
时间窗: At Day 28 (1 Cycle)
次要结局
未报告次要终点