A Phase 1 Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Ovarian and Cervical Carcinoma, Sarcomas, and Neuroendocrine Tumors Including Small Cell Lung Cancer and Merkel Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 96
- 试验地点
- 14
- 主要终点
- Determine maximun tolerated dose (MTD) of FF-10850
研究概览
简要总结
To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in patients with advanced solid tumors including Merkel Cell Carcinoma
详细描述
Dose-escalation Phase: Approximately 48 patients are planned for the dose-escalation phase, with at least 6 patients treated at the RP2D.
Cohort Expansion Phase: Two additional cohorts are planned. Cohort E1: advanced ovarian cancer and Cohort E5 Merkel cell carcinoma. Each cohort will be treated at the RP2D.
In each cohort, FF-10850 will be administered intravenously (IV) until progression of disease, observation of unacceptable AEs, or, after discussion between the Investigator and the Medical Monitor, changes in the patient's condition that prevent further study participation. A sufficient number of cohorts will be enrolled to identify the RP2D.
There will be 3 initial dose levels in this study. FF-10850 will be diluted and infused over 60 minutes.
Approximately 96 patients are planned for the entire trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
None, open label
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 must meet all the following criteria to participate in the study:
- •Males and females ≥ 18 years of age
- •Dose-escalation phase: Histologically or cytologically confirmed metastatic and/or unresectable solid tumor, relapsed or refractory to standard therapy, or for which no standard therapy is available that is expected to improve survival by at least 3 months
- •At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter), radiotherapy, major surgery, or experimental treatment, and recovered from all acute toxicities (≤ Grade 1), prior to the first dose of FF-10850
- •Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
- •Life expectancy of ≥ 3 months
- •Adequate hematologic parameters without ongoing transfusion support:
- •Hemoglobin (Hb) ≥ 9 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L
- •Platelets ≥ 100 × 109 cells/L
- •Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 50 mL/minute by either the Cockcroft-Gault formula or as measured by a 24-hour urine collection
- •Total bilirubin ≤ 2 × ULN unless due to Gilbert's disease; patients with Gilbert's disease who have a total bilirubin > 6 mg/dL are to be excluded
- •ALT and AST ≤ 2.5 times ULN, or < 5 × ULN for patients with liver metastases
- •QT interval corrected for rate (QT interval corrected for rate using Fridericia's Correction Formula, QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening and confirmed pre-treatment on Cycle 1 Day
- •Patient must be willing to undergo a tumor biopsy, if the patient has a biopsy-accessible tumor
排除标准
- •Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
- •History of severe hypersensitivity reactions to topotecan
- •Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome
- •Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, except for antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care
- •Active central nervous system (CNS) malignant disease in patients with a history of CNS malignancy. Patients with previously treated stable brain metastases are allowed if they have been stable off steroid therapy for at least 4 weeks.
- •Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
- •Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
- •Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
- •Pregnant or breast-feeding
研究组 & 干预措施
Cohort E5: Treatment at Recommended Phase 2 Dose (RP2D)
For patients with advanced Merkel cell carcinoma: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
干预措施: FF-10850 Topotecan Liposome Injection (Drug)
Cohort 3: Treatment at Dose Level 3
FF-10850 Topotecan Liposome Injection, Dose Level 3 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
干预措施: FF-10850 Topotecan Liposome Injection (Drug)
Cohort 2: Treatment at Dose Level 2
FF-10850 Topotecan Liposome Injection, Dose Level 2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
干预措施: FF-10850 Topotecan Liposome Injection (Drug)
Cohort E1: Treatment at Recommended Phase 2 Dose (RP2D)
For patients with advanced ovarian cancer: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
干预措施: FF-10850 Topotecan Liposome Injection (Drug)
Cohort 1: Treatment at Dose Level 1
FF-10850 Topotecan Liposome Injection, Dose Level 1 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
干预措施: FF-10850 Topotecan Liposome Injection (Drug)
结局指标
主要结局
Determine maximun tolerated dose (MTD) of FF-10850
时间窗: 4 years
MTD is defined as the next lower dose of a cohort where patients experienced a DLT
Identify dose-limiting toxicities (DLT) of FF-10850
时间窗: 4 years
DLT is defined as any adverse event at least possibly related to FF-10850, and meeting specified DLT criteria
Determine recommended Phase 2 dose (RP2D) FF-10850
时间窗: 4 years
The highest dose level below the dose level eliciting DLT in ≥ 2 patients will be declared the MTD. The RP2D will be chosen based on the MTD or on PK and biological activity if an MTD has not been determined.
Determine incidence of Treatment Emergent Adverse Events
时间窗: 4 years
Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)
次要结局
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL(4 years)
- Determine objective response rate (ORR)(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT(4 years)
- Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Vss(4 years)
- Evaluate progression-free survival (PFS)(4 years)
- Evaluate overall survival (OS) (expansion cohorts only)(4 years)
- Determine the duration of response (DOR)(4 years)
- Determine the time to progression (TTP)(4 years)