A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, PK, and PD Study of CNF2024 Administered Orally Twice Weekly for 3 Weeks of a 4 Week Course or Twice Weekly for 4 Weeks of a 4 Week Course to Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- effect on pharmacodynamic biomarkers
研究概览
简要总结
This is an open-label, multicenter, dose-escalation, safety, pharmacokinetics, and pharmacodynamics study.
详细描述
Heat shock protein 90 (Hsp90) is an ubiquitous molecular chaperone protein that is involved in folding, activation, and assembly of many proteins, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. In cancer cells that are dependent upon Hsp90 client proteins, the degree to which clients are inhibited correlates closely with induction of growth inhibition and apoptosis with Hsp90 inhibitory drugs. The active pharmaceutical ingredient of CNF2024, CF1983 mesylate, is a synthetic, new chemical entity designed to inhibit Hsp90. CF1983 hada strong affinity for tumor derived Hsp90 and weaker affinity for Hsp90 isolated from normal cells or recombinant Hsp90.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed solid tumor which has failed standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy) or for which effective therapy is not available
- •At least 18 years of age
- •Hematology: Absolute neutrophil count (ANC) > 1500 cells/mm3, platelet count > 100,000 cells/mm3 and hemoglobin >= 9 gm/L
- •Hepatic: Bilirubin < 1.5 X upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN. Patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN.
- •Renal: Serum creatinine levels < 2.0 mg/dL or creatinine clearance > 60 mL/min
- •Coagulation: international normalized ratio (INR) < 1.5 times normal
- •Adrenal: Normal plasma cortisol and adrenocorticotropic hormone (ACTH) levels
- •Normal electrocardiogram (ECG) with QTc <= 450 msec for men and <= 470 msec for women
- •Estimated life expectancy of at least 3 months as determined by the Investigator
- •Eastern Cooperative Oncology Group (ECOG) performance status <= 2
- •Male and female patients of childbearing potential must practice effective double-barrier contraception during the study and continue contraception for 3 months after their last dose of study drug. Male patients must agree to not have intercourse with pregnant or nursing women during the study and for 3 months after their last dose of study drug, unless using double-barrier contraception. The only exceptions to double-barrier contraception are: Patient or partner is surgically sterile,female patient is postmenopausal for at least 1 year before screening or patient abstains from sexual intercourse, at the discretion of the Investigator
排除标准
- •Pregnant or nursing women, women of child-bearing age not using reliable means of contraception.
- •Radiotherapy or chemotherapy within the previous 28 days. Recovery to Grade 1 or less from chemotherapy-induced toxic effect, except alopecia, is required.
- •Participation in any investigational drug study within 28 days prior to CNF2024 administration
- •Active infection requiring intravenous antibiotic treatment
- •Patients with second malignancy requiring active treatment (except hormonal therapy)
- •Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure)
- •Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis
- •Problems with swallowing or malabsorption
- •Chronic diarrhea (excess of 2-3 stools/day above normal frequency)
- •Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis
- •Major surgery of the stomach or small intestine
- •Adrenal dysfunction > Grade 2
- •Patients with diabetes (your doctor will discuss if you are eligible for this study)
研究组 & 干预措施
Dosing Schedule 1
Starting dose of 25 mg, with dosing twice a week for 3 weeks out of a 4-week course (Schedule 1). Dosing for schedule 1 is currently closed.
干预措施: CNF2024 (Drug)
Dosing Schedule 2
Starting dose of 600 mg, with dosing twice a week for 4 weeks out of a 4-week course (without drug holidays; Schedule 2).
干预措施: CNF2024 (Drug)
结局指标
主要结局
effect on pharmacodynamic biomarkers
时间窗: Dosing period
antitumor activity
时间窗: At screening and after every 2 courses
pharmacokinetic profile
时间窗: Dosing period
To determine the maximum tolerated dose (MTD)
时间窗: Dose escalation will proceed according to the predetermined scheme until the stopping dose (dose > MTD) is reached due to dose limiting toxicities (DLT) occurring during the first 4-week course of treatment.
To determine the safety profile
时间窗: Study duration
次要结局
未报告次要终点