A Phase I Dose-finding and Pharmacokinetic Study of RTA 402 (CDDOMe) Administered Orally for 21 Days of a 28-day Cycle in Patients With Advanced Solid Tumors or Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 47
- 试验地点
- 3
- 主要终点
- To determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of Bardoxolone methyl Capsules
研究概览
简要总结
This study assesses the tolerability, safety, efficacy and pharmacokinetics of Bardoxolone methyl (RTA 402) in advanced solid tumors and lymphoid malignancies.
详细描述
Bardoxolone methyl (RTA 402) is a synthetic triterpenoid that has demonstrated significant in vivo single agent anti-cancer activity. This is an open-label phase I dose-escalation study of Bardoxolone methyl (RTA 402) administered orally for the first 21 days of a 28-day cycle.
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
- •Histopathological documentation of solid tumor or lymphoid malignancy.
- •Advanced or metastatic cancer that is either refractory to or have relapsed after standard-of-care curative or survival-prolonging therapy, or for whom no such therapies exist.
- •ECOG performance status of less than or equal to 2
- •Adequate liver and renal function as documented by the following laboratory test results within 14 days of starting therapy: total bilirubin ≤ 1.5 mg/dL; AST (SGOT) and ALT(SGPT) ≤ 2.5 ULN or ≤ 5 ULN if liver is involved by tumor; serum creatinine ≤2.0 mg/dL OR creatinine clearance >60 mL/min.
- •Adequate bone marrow function as documented by the following laboratory test results within 14 days of starting therapy: platelets greater than 100,000/mm3, absolute granulocyte count greater than 1,500/mm3, hemoglobin greater than or equal to 8.0 g/dl.
- •Completion of prior chemotherapy, hormonal therapy, radiation therapy, biological therapy, or other investigational cancer therapy, for at least 4 weeks prior to study entry and must have recovered from all acute side effects (to CTC grade 1 or less) prior to initiation of RTA
- •Patients who were receiving mitomycin C or nitrosoureas must be 6 weeks from the last administration of chemotherapy.
- •Agree to practice effective contraception during the entire study period.
- •Life expectancy of more than 3 months
- •Able and willing to sign the informed consent form.
- •Willing and able to self-administer orally and document all doses of RTA 402 ingested.
排除标准
- •Active brain metastases or primary CNS malignancies.
- •Pregnant or breast feeding
- •Clinically significant illnesses including, but not limited to: Uncontrolled diabetes; Active or uncontrolled infection; Acute or chronic liver disease; Confirmed diagnosis of HIV infection; Uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
- •Psychiatric illness that would limit compliance with study requirements.
研究组 & 干预措施
Bardoxolone methyl capsules
Bardoxolone methyl to be taken orally for 21 consecutive days, once a day, in the morning prior to food intake.
Patients to continue to receive treatment for the first 21 days of each 28-day cycle until they experience intolerable toxicity, show evidence of disease progression, or receive a maximum of 18 cycles (18 months).
干预措施: Bardoxolone methyl (Drug)
结局指标
主要结局
To determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of Bardoxolone methyl Capsules
时间窗: 28 day cycles, with a maximum of 18 cycles (18 months)
To characterize the pharmacokinetics of Bardoxolone methyl in this patient population.
时间窗: 28 day cycles, with a maximum of 18 cycles (18 months)
次要结局
- To determine the in vivo molecular and biological effects.(28 day cycles, with a maximum of 18 cycles (18 months))
- To document any preliminary antitumor activity.(28 day cycles, with a maximum of 18 cycles (18 months))
- To correlate the biological activity of RTA 402 with drug concentration in plasma and blood cellular elements.(28 day cycles, with a maximum of 18 cycles (18 months))