A Phase I Study of Triapine® in Combination With Radiation Therapy in Locally Advanced Pancreas Cancer
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 side effects and best dose of 3-AP when given together with radiation therapy in treating patients with stage III pancreatic cancer that cannot be removed by surgery.
3-AP may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. 3-AP may make tumor cells more sensitive to radiation therapy. Giving 3-AP together with radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximal tolerable dose (MTD) of 3-AP administered in combination with radiation therapy (XRT) in patients with locally advanced pancreatic carcinomas.
SECONDARY OBJECTIVES:
I. To document the therapeutic response of this combination in patients with locally advanced pancreatic carcinomas.
II. To establish radiographic correlates using secretin stimulated magnetic resonance cholangiopancreatography (MRCP) and dynamic contrast enhanced magnetic resonance imaging (MRI).
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 adenocarcinoma of the pancreas
- •Unresectable nonmetastatic (stage III) disease
- •ECOG performance status 0-2
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Total bilirubin ≤ 2 times upper limit of normal (ULN)
- •AST/ALT ≤ 3 times ULN
- •Creatinine normal ORcreatinine 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®) or other agents used in study
- •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 situations that would complicate compliance with study treatment
- •No pulmonary disease (i.e., dyspnea at rest, requiring supplemental oxygen, or baseline oxygen saturation < 92%)
- •No prior chemotherapy or radiotherapy
- •No concurrent antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational agents
- •No other concurrent anticancer agents or therapies
排除标准
- 未提供
研究组 & 干预措施
Treatment (triapine, radiation therapy)
Patients undergo radiotherapy once daily, 5 days a week, for approximately 5.5 weeks (a total of 28 fractions). Patients also receive 3-AP (Triapine) IV over 2 hours 3 days a week every other week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine) until the maximum tolerated dose (MTD) is determined.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (triapine, radiation therapy)
Patients undergo radiotherapy once daily, 5 days a week, for approximately 5.5 weeks (a total of 28 fractions). Patients also receive 3-AP (Triapine) IV over 2 hours 3 days a week every other week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine) until the maximum tolerated dose (MTD) is determined.
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 3-4 hours after each 3-AP infusion during the first week of treatment
MTD will be the dose at which 1 or fewer patients (less than or equal to 1/6) experiences a DLT during the treatment cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing DLT. DLT will be defined as greater than or equal to Grade 3 non-hematologic or greater than or equal to Grade 4 hematologic adverse event with the following exceptions: greater than or equal to Grade 3 nausea and greater than or equal to Grade 3 vomiting that improves with antiemetic therapy greater than or equal to Grade 3 diarrhea that improves with Lomotil.
次要结局
- Therapeutic response as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST)(CT scans at baseline and 4 weeks from end of therapy and then every 2 months for 1 year from start of therapy. Confirmatory scans will also be obtained 2 months following initial documentation of an objective response.)
- Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP(Immediately before and after 3-AP on the first and last day of treatment)
- Radiographic correlates using secretin-stimulated MRCP and dynamic contrast enhanced MRI(Prior to treatment (baseline), 2 weeks within and 4 weeks after combined-modality therapy)