A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 145
- 主要终点
- Safety and tolerability of OPB-111077
研究概览
简要总结
The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer.
详细描述
The secondary objective of this study is to investigate the pharmacokinetic properties of OPB-111077; the pharmacodynamic effects of OPB-111077; the antitumor activity of OPB-111077 as assessed by RECIST or IMWG Uniform Response Criteria; and to explore whether PET responses correlate with other measures of clinical response.
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
- •Pathologically and/or cytologically confirmed advanced malignancy that is refractory to standard therapy or for which there are no standard treatment options available
- •For oral or intravenous anticancer therapies, at least 4 weeks or 5 half-lives, whichever is shorter, need to have elapsed since the last dose
- •Recovery from adverse effects of prior therapy at time of enrollment to
- •o ≤ Grade 1 (excluding alopecia)
- •Agreement to forego any other chemotherapy, immunotherapy, radiotherapy, or investigational drug while enrolled on this trial except hormonal therapy for prostate cancer or radiotherapy for symptomatic bone metastases known to be present at Screening
- •Male or female subjects aged ≥ 18 years
- •ECOG performance status ≤ 2
- •Adequate organ function
- •Life expectancy of ≥ 3 months following trial entry
- •For women of childbearing potential, a negative serum pregnancy test result at Screening
- •For women of childbearing potential or men whose sexual partners are women of childbearing potential, agreement to use 2 methods of adequate contraception prior to trial entry, for the duration of the trial, and for 90 days after the last dose of trial medication
- •Signed and dated IRB-approved informed consent prior to any performance of protocol-specific screening procedures
排除标准
- •Uncontrolled concurrent illness, including but not limited to: ongoing or active infection; uncontrolled heart, liver, kidney, or endocrine disorder
- •Altered mental status, psychiatric illness, or social situation that would limit compliance with trial requirements and/or obscure trial results
- •Immunocompromised state
- •Known or evidence of chronic viral hepatitis (hepatitis B or C virus)
- •Untreated or symptomatic brain metastasis, or subjects with leptomeningeal disease
- •Inability to swallow oral meds or gastrointestinal disorder that might interfere with absorption of oral drugs
- •Major surgery within 28 days of first receipt of trial drug
- •Nursing or pregnant women
- •≥ Grade 1 neuropathy with pain or > Grade 2 neuropathy without pain (subjects with neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable without pain may be included)
- •Food-effect sub-study (Part B) only: Pathologies or medical histories that might impair absorption and elimination.
- •PET scan sub-study (Part C) only: Uncontrollable blood glucose or intolerance to PET scan procedures.
研究组 & 干预措施
OPB-111077
In escalation stage of study, treatment with a once daily dose of OPB-111077 during cycles 1 and 2 on day 1, followed by 2-day treatment free interval, and then resuming daily dosing on day 4 through day 28. For cycle 3 and beyond, OPB-111077 will be administered for 28 continuous days per cycle until MTD is reached.
In expansion portion of study, established dose of 250mg administered once daily for 28 consecutive days for each cycle. Patient in expansion are defined as those who meet eligibility criteria and have a diagnosed malignancy that is presumed to be susceptible to inhibition by OPB-111077
干预措施: OPB-111077 (Drug)
结局指标
主要结局
Safety and tolerability of OPB-111077
时间窗: 28 Days
AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status
次要结局
- To determine the pharmacokinetics of OPB-111077(28 Days)
- Pharmacodynamic profile(28 Days)
- Antitumor effects(Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.)
- To determine the MTD of OPB-111077(Within the first cycle [28 days].)
- PET Sub-study (Part C)(2 weeks)
- Food-effect Sub-study (Part B)(11 days)