A Phase 1 Study to Investigate the Mass Balance of [14C]-Nanatinostat and to Evaluate the Relative Bioavailability of Nanatinostat in Patients With Selected Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameter: Fraction of the administered dose in comparison with a standard (Frel) [Part B]
研究概览
简要总结
This study will determine how nanatinostat is absorbed, modified, and removed from the body (Part A), the amount of nanatinostat that becomes available to the body (Part B), and will evaluate the safety and tolerability of nanatinostat (Part C) in patients with advanced cancers.
详细描述
This is a Phase 1, open-label, 3-part study evaluating the mass balance, pharmacokinetics, and metabolism of nanatinostat following a single oral dose of [14C]-nanatinostat for Part A, evaluating relative bioavailability of nanatinostat mesylate and nanatinostat (free base) tablets after coadministration with valganciclovir in patients with advanced stage cancers for Part B, and evaluating the safety and antitumor activity of nanatinostat for Part C.
The study was terminated prematurely and did not reach its target enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 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
- •Have histologically confirmed advanced stage cancers (excluding gastrointestinal tumors), have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment, and have no available treatment with curative intent.
- •Eastern Cooperative Oncology Group Performance Status of ≤2 at Screening.
- •Body mass index ≥18.5 but ≤30.0 kg/m2 at Screening.
- •Adequate bone marrow, liver, and kidney function.
排除标准
- •Presence of active central nervous system and/or leptomeningeal disease.
- •Anticancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy, or use of other investigational agents within 4 weeks before study entry.
- •Inability to take or tolerate oral medication.
- •Any gastrointestinal, liver, or kidney condition that may affect drug absorption and metabolism.
- •Active infection requiring systemic therapy.
- •Has received radiolabeled material <12 months (excluding that required for imaging) prior to study entry.
研究组 & 干预措施
Part A: [14C]-Nanatinostat
干预措施: [14C]-Nanatinostat (Drug)
Part B (Treatment A): Nanatinostat (free base) tablets in combination with Valganciclovir
Patients will be randomized into 2 treatment sequences (AB and BA) in Periods 1 and 2. Each treatment period is 24 hours.
干预措施: Nanatinostat (free base) tablets in combination with Valganciclovir (Drug)
Part B (Treatment B): Nanatinostat mesylate tablets in combination with Valganciclovir
Patients will be randomized into 2 treatment sequences (AB and BA) in Periods 1 and 2. Each treatment period is 24 hours.
干预措施: Nanatinostat mesylate tablets in combination with Valganciclovir (Drug)
Part C: Single-agent Nanatinostat (free base) tablets
干预措施: Single-agent Nanatinostat (free base) tablets (Drug)
结局指标
主要结局
Pharmacokinetic Parameter: Fraction of the administered dose in comparison with a standard (Frel) [Part B]
时间窗: 8 weeks after the last discharge visit in Part B
The amount of radioactivity in excreta [Part A]
时间窗: 8 weeks after the last discharge visit in Part A
Pharmacokinetic Parameter: area under the plasma concentration versus time curve (AUC) [Part B]
时间窗: 8 weeks after the last discharge visit in Part B
Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part B]
时间窗: 8 weeks after the last discharge visit in Part B
Incidence of adverse events and serious adverse events [Part C]
时间窗: 28 days after the last dose of study treatment in Part C
Pharmacokinetic Parameter: time to maximum observed plasma concentration (Tmax) [Part B]
时间窗: 8 weeks after the last discharge visit in Part B
次要结局
- Duration of Response (DOR) [Part C](Approximately 1 year)
- Disease Control Rate (DCR) [Part C](Approximately 1 year)
- Major radioactive peak/metabolites in urine and fecal radiochromatograms as a percentage of the radioactive dose [Part A](8 weeks after the last discharge visit in Part A)
- Time to Response (TTR) [Part C](Approximately 1 year)
- Incidence of adverse events and serious adverse events [Parts A and B](Up to 7 days after the last discharge visit)
- Incidence of clinically significant changes in selected safety assessments [Parts A and B](Up to 7 days after the last discharge visit)
- Pharmacokinetic Parameter: elimination half-life (t1/2) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: apparent total clearance (CL/F) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: apparent volume of distribution during terminal phase (Vz/F) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: elimination rate constant from the central compartment (Kel) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: maximum plasma concentration (Cmax) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: time to maximum observed plasma concentration (Tmax) [Part A](8 weeks after the last discharge visit in Part A)
- The ratio of total radioactivity in blood relative to plasma [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: area under the plasma concentration versus time curve (AUC) [Part A](8 weeks after the last discharge visit in Part A)
- Pharmacokinetic Parameter: elimination half-life (t1/2) [Part B](8 weeks after the last discharge visit in Part B)
- Pharmacokinetic Parameter: metabolite-to-parent ratio [Part B](8 weeks after the last discharge visit in Part B)
- [14C]-metabolic profile and identification of metabolites in plasma [Part A](8 weeks after the last discharge visit in Part A)
- Objective Response Rate (ORR) [Part C](Approximately 1 year)