A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of Pazopanib and Vorinostat
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of pazopanib and vorinostat that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.
详细描述
Study Drugs:
Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.
Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, up to 12 dose levels of pazopanib and vorinostat will be tested. Three (3) to 6 participants will be enrolled at each dose level of the combination of pazopanib and vorinostat. The first group of participants will receive the lowest dose level of pazopanib and vorinostat. Each new group(s) will receive a higher combination dose of pazopanib and vorinostat than the group before it, if no intolerable side effects were seen. Participants may be enrolled on 1-3 similar dose levels of pazopanib and vorinostat at the same time. You will be assigned to a dose level based on when you joined this study. This will continue until the highest tolerable dose(s) of the study drug combination is found.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available.
- •Patients must have measurable or evaluable disease, as defined by RECIST 1.
- •Men or women aged >/= 18 years. However, patients who are 13 years old or older and have more than 45 kg of body weight will be eligible after consultation with their pediatric attending since the doses of these agents are the fixed doses.
- •Women of child-bearing potential and men must agree to use adequate contraception.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ functions: Neutrophils > 1000/uL, Platelets >/= 75,000/uL, Total bilirubin </= 2 x upper limit of normal (ULN) (upper limit of normal), ALT </= 2.5 x ULN or </= 5 x ULN if liver metastases persist, Serum creatinine < 2 x ULN
- •Patients with either previous vascular endothelial growth factor (VEGF) inhibition based treatment or previous vorinostat based treatment are eligible. However, patients who received both VEGF and histone deacetylase (HDAC) inhibition simultaneously are ineligible.
- •Specific to the cohorts as designed to enroll patients with TP53 mutations: TP53 mutations are identified by next-generation sequencing in a chemiluminescence immunoassay analyzer (CLIA)-certified laboratory prior to screening.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), or unstable angina pectoris.
- •Inadequately controlled hypertension (defined as systolic blood pressure >or = 140 and/or diastolic blood pressure > or = 90 mmHg on antihypertensive medications), any prior history of hypertensive crisis or hypertensive encephalopathy, and history of myocardial infarction or unstable angina within 6 months prior to study enrollment.
- •History of stroke or transient ischemic attack within 6 months prior to study enrollment.
- •Major surgical procedure within 28 days prior to study enrollment.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
- •History of allergic reactions to the study drugs, their analogs or any component of the products.
- •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 5 half-lives for targeted agents with half lives and pharmacodynamic effects lasting less than 5 days (that includes but is not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents). Palliative radiation immediately before or during the study is acceptable provided there is evaluable disease that has not been radiated.
- •Urine for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
- •Patients with clinical bleeding, active gastric or duodenal ulcer.
- •Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids.
- •Concurrent use of antiarrythmics or contraindicated medications (including, but not limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin, thioridazine).
研究组 & 干预措施
Pazopanib + Vorinostat
Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily
干预措施: Pazopanib (Drug)
Pazopanib + Vorinostat
Starting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily
干预措施: Vorinostat (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of Pazopanib and Vorinostat
时间窗: 28 days
Maximum tolerated dose defined by dose limiting toxicities (DLTs) that occur in the first 28 days. . Non-hematological toxicities are graded by using NCI CTCAE v4.0 toxicity criteria and DLT defined as treatment-related grade 3 or greater non-hematological toxicity other than nausea, vomiting, fatigue, or hypertension, drug-related grade 3 or greater electrolyte abnormalities that do not return to ≤ grade 1 or baseline within 72 hours, grade 3 nausea and vomiting related to study drug treatment that is not controlled at 72 hours despite appropriate antiemetic therapy, or grade 4 fatigue or hypertension related to study drug therapy.
次要结局
未报告次要终点