A Phase I Study of a Prolonged Infusion of Triapine in Combination With a Fixed Dose Rate of Gemcitabine in Patients With Advanced Solid Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
研究概览
简要总结
This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximal tolerable dose (MTD) of 3-AP administered as a 24 hour infusion in combination with and fixed-dose gemcitabine hydrochloride (GEM) in patients with advanced solid tumors or lymphomas.
SECONDARY OBJECTIVES:
I. To define the qualitative and quantitative toxicities of the 3-AP/GEM combination in regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of this combination in those patients when possible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histologically or cytologically confirmed advanced solid tumors or lymphoma
- •Disease considered incurable using standard treatment
- •ECOG performance status ≤ 2
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Total bilirubin normal
- •AST/ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception prior to and during study treatment
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to 3-AP (Triapine®) and/or gemcitabine hydrochloride
- •No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
- •No pulmonary disease (e.g., dyspnea at rest, supplemental oxygen requirement, or baseline oxygen saturation < 92%)
- •Prior gemcitabine hydrochloride allowed if given as a standard 30-minute infusion
- •At least 4 weeks since prior gemcitabine hydrochloride
- •Patient may have received < 2 lines of chemotherapy in the metastatic setting
- •No prior 3-AP (Triapine®) or fixed-dose gemcitabine hydrochloride
- •At least 6 weeks since prior nitrosoureas or mitomycin C
- •More than 3 weeks since prior radiotherapy
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy in HIV-positive patients
- •No other concurrent anticancer agents or therapies
排除标准
- 未提供
研究组 & 干预措施
Treatment (gemcitabine hydrochloride, triapine)
Patients receive 3-AP (Triapineî) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: gemcitabine hydrochloride (Drug)
Treatment (gemcitabine hydrochloride, triapine)
Patients receive 3-AP (Triapineî) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: triapine (Drug)
结局指标
主要结局
MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
时间窗: Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment
MTD is the maximum dose level with fewer than 2 of 3/6 patients experiencing DLT. The study uses standard method phase I design of dose escalation. DLT will be defined as greater or equal to Grade 3 non-hematologic or greater or equal to Grade 4 hematologic adverse event EXCEPT: greater or equal to Grade 3 nausea and greater or equal to Grade 3 vomiting that improves with antiemetic therapy; greater or equal to Grade 3 diarrhea that improves with Lomotil; and greater or equal to Grade 4 Neutropenia that recovers to less or equal to Grade 3 within 7 days of first identification.
次要结局
- Toxicity as assessed using the NCI Common Toxicity Criteria, Version 3.0(Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment and monitored until disease progression or for a maximum of 24 months following termination of treatment)
- Therapeutic response(Tumor and radiologic measurements every 8 weeks from start of treatment. In addition to a baseline scan, confirmatory scans will also be obtained 8 weeks following initial documentation of an objective response.)
- Duration of overall response(Baseline until disease progression or for a maximum of 24 months following termination of treatment.)
- Duration of stable disease(Baseline until disease progression or for a maximum of 24 months following termination of treatment.)
- Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP(PMBCs isolated immediately before and after 3-AP infusion (day 1), but before GEM is started on (day 2) on both course 1 and course 2 of treatment)
- Pharmacokinetics as assessed by steady state concentration (Css) of 3-AP in serum(On the first day of infusion (course 1 only) during the last 4 hours of 3-AP infusion)