A Phase 1/2a, Dose-escalation Study of FF-10502-01 for the Treatment of Advanced Solid Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 4
- 主要终点
- Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
A Phase 1/2a, dose-escalation study of FF-10502-01 in Patients with Advanced Solid Tumors and Lymphomas. A total of up to 9 cohorts will be enrolled in Phase 1 to establish the Maximum Tolerated Dose (MTD). Phase 2 will consist of 2 cohorts: Cohort 1 will include subjects with Pancreatic Cancer. Cohort 2 will include subjects with another tumor type enrolled in the Phase 1 dose-escalation phase who have demonstrated Clinical Benefit by Week 16.
详细描述
Subjects will receive doses of FF-10502-01 intravenously (IV) weekly for three weeks, repeated every 28 days (= 1 cycle). Disease assessments, based on computed tomography (CT), magnetic resonance image (MRI), and, for lymphoma, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans, will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease (PD). Subjects who demonstrate clinical benefit will be allowed to continue therapy with FF-10502-01 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Males and females ≥ 18 years of age
- •Histologically or cytologically confirmed advanced or metastatic solid tumor or l lymphoma, that is refractory to standard therapy, relapsed after standard therapy, or for which no standard therapy available that is expected to improve survival by at least three months
- •At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, whichever is shorter), radiotherapy, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1)
- •Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2
- •Life expectancy of ≥ 3 months
- •Adequate hematologic parameters without ongoing transfusional support:
- •Hemoglobin (Hb) ≥ 9 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L
- •Platelets ≥ 100 x 109 cells/L
- •Adequate renal and hepatic function:
- •Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula
- •Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease
- •Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ( ≤ 2.5 times ULN, or < 5 times ULN for subjects with liver metastases
- •QT interval corrected for rate (QTc) ≤ 480 msec on the electrocardiogram (ECG) obtained at Screening
- •Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of study treatment.
- •Ability to provide written informed consent
排除标准
- •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
- •Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials 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 subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed.
- •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
Phase 2a, Cohort 13, Urothelial carcinoma
FF-10502-01 at 90mg/m2 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle.
干预措施: FF-10502-01 (Drug)
Phase 1, Cohorts 1-9
FF-10502-01 administered intravenously (IV) on Days 1, 8, and 15 of a 28-day cycle. Dosing by cohort: Cohort 1, 8mg/m2; Cohort 2, 12mg/m2; Cohort 3, 18mg/m2, Cohort 4, 27mg/m2; Cohort 5, 40mg/m2; Cohort 6, 60mg/m2; Cohort 7, 90mg/m2; Cohort 8, 135mg/m2; Cohort 9, 100mg/m2.
干预措施: FF-10502-01 (Drug)
Phase 2a, Cohort 10, Advanced solid tumors
FF-10502-01 at 90mg/m2 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle.
干预措施: FF-10502-01 (Drug)
Phase 2a, Cohort 11, Cholangiocarcinoma
FF-10502-01 at 90mg/m2 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle.
干预措施: FF-10502-01 (Drug)
Phase 2a, Cohort 12, Gall bladder carcinoma
FF-10502-01 at 90mg/m2 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle.
干预措施: FF-10502-01 (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
时间窗: 33 Months
Safety and tolerability assessed by adverse events (AEs), and serious adverse events. (SAEs)
Number of Subjects With Treatment Emergent Adverse Events (TEAE)
时间窗: Each patient was followed from baseline through the treatment period (maximum treatment period up to 38 months) until long-term follow-up was completed (6 mos post end of study) or patient discontinued either by withdrawal, progressive disease or death.
Safety and tolerability assessed by number of subjects with adverse events (AEs), and serious adverse events. (SAEs)
次要结局
- Determination of overall response rates(Responses assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug (every 28 days=1 cycle).)
- Determination of duration of response.(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug)
- Evaluate overall survival (OS)(Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug)
- Evaluate FF-10502-01 incorporation into whole blood cellular DNA by LC-MS/MS as a pharmacodynamic marker(Assessed at Cycle 1 Day 1, Cycle 1 Day , Cycle 1 Day 15, Cycle 1, Day 22, Cycle 2 Day 1, at the end of Cycle 2 and ever 2 cycles thereafter up to 24 weeks.)
- Determination of duration of stable disease (SD) as measured from time of 1st evidence of response to time of 1st evidence of progressive disease as measured by CT or MRI.(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug)
- Evaluate progression-free survival (PFS)(Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug)
- Evaluate the mean plasma concentrations of FF-10502-01(Assessed at Cycle 1 Day 1, and Cycle 1 Day 15)
- Median Number of Days of Stable Disease (SD)(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Number of Subjects With Overall Response Rates (ORR)(Responses assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug (every 28 days=1 cycle), up to 38 months)
- Number of Subjects With Objective Response (OR) Events(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Median Number of Days of Objective Response (OR)(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Number of Subjects With Stable Disease (SD) Events(Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Number of Subjects With Progression-free Survival (PFS) Events(Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Median Number of Days of Progression-free Survival (PFS)(Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Number of Subjects With Overall Survival (OS) Events(Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)
- Median Number of Days of Overall Survival (OS)(Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug, up to 38 months)