A Phase 1 Dose-Escalation Study of the Safety andPharmacokinetics of Daily OCID 4681-S-01 Administered Orally to Subjects with Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- ? Evaluate the safety and tolerability of daily oral administration of OCID
研究概览
简要总结
OCID 4681–S-01 is an HDAC inhibitor which is believed to have significant anti-tumor activity. Based on preclinical studies result, OCID 4681-S-01 is known to promote histone acetylation and increase expression of the growth suppressor gene p21, which have been shown to increase cellular apoptosis and inhibit growth in tumor cells. These properties make OCID 4681-S-01 a good candidate for testing in humans for anti-cancer activity. Chemically, OCID 4681-S-01 is (E)-N-(2-aminophenyl)-4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-en-1-yl)benzamide hydrochloride. Vorinostat, a hydroxamate-based inhibitor, was the first HDACi to be approved by the Food and Drug Administration (FDA) in October 2006 for the treatment of refractory Cutaneous T-Cell lymphoma for patients who had received two or more prior systemic therapies. The trial is conducted in 3 sites in India. The sites would enroll up to 36 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists.
- •2 The subject is greater than or equal to 18 years old.
- •3 The subject has an Eastern Cooperative Oncology Group ECOG performance status of 0 to 2 Appendix B 4 Subject has a life expectancy of greater than 3 months.
- •5 The subject has adequate organ and marrow function as follows Absolute neutrophil count ANC greater than or equal 1500mm
- •Platelets greater than or equal 100,000mm
- •Hemoglobin greater than or equal 10 g per dL, with no transfusions within the last seven days.
- •Bilirubin less than or equal 1.5 the upper limit of normal ULN.
- •Serum creatinine less than or equal 1.5 ULN or calculated creatinine clearance greater than or equal 60 mL per min.
- •Alanine aminotransferase ALT and aspartate aminotransferase AST less than or equal 2.5 ULN if no liver involvement, or less than or equal 5 ULN with liver involvement.
- •6 The subject is able to swallow and tolerate oral medications such as capsules.
- •7 The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
- •8 Sexually active subjects men and women must agree to use medicallyaccepted barrier methods of contraception eg, male condom, female condom, or diaphragm with spermicidal gel during the course of the study and for 3 months after the last dose of study drugs, even if oral contraceptives are also used.
- •All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control.
- •9 Women of childbearing potential must have a negative pregnancy test at screening.
- •Women of childbearing potential include any woman who has experienced menarche and who has not undergone successful surgical sterilization hysterectomy, bilateral tubal ligation, or bilateral oophorectomy or is not postmenopausal.
- •Post menopause is defined as Amenorrhea greater than or equal 12 consecutive months without another cause or For women with irregular menstrual periods and on hormone replacement therapy, a documented serum follicle stimulating hormone FSH level 35 mIU per mL.
排除标准
- •1 The subject has received cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents eg, cytokines or antibodies within 3 weeks, or nitrosoureas or mitomycin C within 6 weeks before the first dose of study treatment.
- •2 The subject has received radiation therapy within 14 days of the first dose of study treatment.
- •Palliative radiation to nonmarrow areas is allowed.
- •3 The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
- •4 The subject has not recovered from toxicity due to all prior therapies ie, return to pretherapy baseline or to Grade 0 or 1 5 The subject has received lifetime radiation to 25 percent of his or her bone marrow before the first dose of study treatment.
- •6 The subject has a primary brain tumor or brain metastases.
- •7 The subject has prothrombin time PT International Normalized Ratio INR or partial thromboplastin time PTT test results at screening that are 1.3 times the laboratory ULN.
- •8 The subject has uncontrolled significant intercurrent illness including, but not limited to ongoing or active infection, history of congestive heart failure within 6 months, uncontrolled hypertension or unstable angina pectoris within 6 months, stroke within 3 months, myocardial infarction within 3 months, or cardiac arrhythmias.
- •9 The subject is pregnant or breastfeeding.
- •10 The subject tests positive for the human immunodeficiency virus HIV, Hepatitis B virus (HBV) or Hepatitis C virus HCV at screening.
- •11 The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
- •12 The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
结局指标
主要结局
? Evaluate the safety and tolerability of daily oral administration of OCID
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
4681-S-01.
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
? Determine the MTD of daily oral administration of OCID 4681-S-01.
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
The primary objectives of this study in patients with solid tumors are as follows:
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
? Determine the safety profile and most common dose-limiting toxicities (DLTs) of daily oral administration of OCID 4861.
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
? Evaluate the plasma pharmacokinetics of daily oral administration of OCID 4681-S-01.
时间窗: Although all subjects may continue to receive study treatment until | experiencing toxicity or disease progression it is estimated that each | subject will participate for an average of 2 to 4 months of treatment with an | additional 1 month of followup.
次要结局
- The secondary objectives of this study are as follows:(• To evaluate tumor response (preliminary antitumor activity) after repeated)