NCT00695448终止1 期
A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK1059615 in Patients With Solid Tumors or Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.
研究概览
简要总结
This is an open-label, multi-center Phase I study conducted to define the recommended Phase 2 dose, toxicity profile, pharmacokinetics and biologically active dose range of GSK1059615.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Written informed consent provided.
- •18 years old or older.
- •Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy or lymphoma that is not responsive to accepted standard therapies or for which there is no standard or curative therapy.
- •Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- •A life expectancy of > 12 weeks.
- •Able to swallow and retain oral medication.
- •A male is eligible to enter and participate in the study if he either:
- •agrees to abstain from sexual intercourse from the first dose of study drug and until 21 days after last dose of study medication, or
- •agrees to use a condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository from the first dose of study drug and until 21 days after last dose of study medication, or
- •is surgically sterile. NOTE: Male patients must use contraception to prevent pregnancy in a female partner and prevent exposure of any partner to semen by any means (refer to protocol).
- •A female is eligible to enroll in the study if she is of:
- •Non-child bearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who is characterized by at least one of the following:
- •Has had a hysterectomy
- •Has had a bilateral oophorectomy (ovariectomy)
- •Has had a bilateral tubal ligation
- •Is post-menopausal (total cessation of menses for ≥ 1 year) Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following from at least 2 weeks prior to the first dose of study drug and until 21 days after last dose of study medication:
- •Use an intrauterine device (IUD) with a documented failure rate of
- •less than 1% per year.
- •Have intercourse only with a vasectomized partner who is sterile
- •and is the sole sexual partner for that woman.
- •Complete abstinence from sexual intercourse.
- •Use double barrier contraception defined as condom with
- •spermicidal jelly, foam, suppository, or film; OR diaphragm with
- •spermicide; OR male condom and diaphragm. NOTE: Oral contraceptives are not reliable due to potential for drug-drug interaction.
- •Adequate organ system function as defined in the protocol.
排除标准
- •Use of an investigational anti-cancer drug within 28 days or 5 half-lives preceding the first dose of GSK
- •Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity are permitted with approval of the GSK medical monitor if administered at least 2 weeks prior to the first dose of study drug.
- •Trastuzumab within the last 4 weeks.
- •Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
- •Prior use of any PI3K inhibitor.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug. (To date there are no known FDA approved drugs chemically related to GSK1059615).
- •Current use of a prohibited medication or requires any of these medications during treatment with GSK1059615 as per protocol.
- •Current use of warfarin for therapeutic anticoagulation.
- •NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted. PT/PTT must meet the inclusion criteria. Patients taking warfarin must have their INR followed closely.
- •Presence of an active gastrointestinal disease or other condition known to interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- •Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia. Patients with stable Grade 2 neuropathy can be enrolled with approval by the GSK Medical Monitor.
- •QTc interval ≥ 480 msecs.
- •History of acute coronary syndromes (including unstable angina and myocardial infarction), atrial fibrillation, coronary angioplasty, or stenting within the past 24 weeks.
- •Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- •Symptomatic or untreated leptomeningeal or brain metastases. Patients previously treated for these conditions who are asymptomatic and off of corticosteroid and P450-inducing anti-epileptic medication for at least 2 months are permitted.
- •Primary malignancy of the central nervous system.
- •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- •Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
- •Nursing female.
研究组 & 干预措施
Cohorts
Experimental
The starting dose is 6mg once daily (QD); dose is to be escalated using a standard 3 + 3 dose escalation scheme.
干预措施: GSK1059615 (Drug)
结局指标
主要结局
Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.
时间窗: 21 days
次要结局
- Pharmacokinetic parameter values for GSK1059615 following single and repeated dosing, including area under the plasma drug concentration curve (AUC), maximum observed plasma drug concentration (Cmax)(21 days)
- time to maximum observed plasma drug concentration, and half-life of GSK1059615.(21 days)
- Metabolic profiling in plasma and urine, and amount excreted in urine (subset of patients).(21 days)
- Tumor response as defined by RECIST in the protocol.(56 days)
- Change from baseline in protein markers in tumor and/or blood.(28 days)
- Blood glucose and insulin levels.(Daily for 28 days)
研究者
研究点 (1)
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