A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0
研究概览
简要总结
Drugs used in chemotherapy, such as irinotecan, oxaliplatin, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells. This phase I trial is studying the side effects and best dose of irinotecan, oxaliplatin, and capecitabine in treating patients with unresectable solid tumors.
详细描述
OBJECTIVES:
I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).
II. To identify any activity of this treatment combination in patients with metastatic cancer.
III. To examine the differences in the toxicity profile, especially pertaining to hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.
IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its metabolites.
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 confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
- •Unresectable disease
- •Willing to provide biologic specimens to determine UGT1A1 genotype
- •No CNS metastases
- •Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9.0 g/dL
- •Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or 7/7 UGT1A1 genotype)
- •AST no greater than 3 times ULN (5 times ULN if there is liver involvement)
- •Creatinine no greater than 1.5 times ULN
- •No New York Heart Association class III or IV heart disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy
- •No uncontrolled infection
- •No seizure disorder
- •No peripheral neuropathy grade 2 or greater
- •More than 4 weeks since prior biologic therapy
- •More than 4 weeks since prior immunotherapy
- •No concurrent immunotherapy
- •No concurrent prophylactic colony-stimulating factor therapy
- •More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- •No other concurrent chemotherapy
- •See Disease Characteristics
- •More than 4 weeks since prior radiotherapy
- •No prior radiotherapy to more than 25% of the bone marrow
- •No concurrent radiotherapy
- •See Disease Characteristics
- •No other concurrent investigational therapy
- •No concurrent sorivudine, brivudine, lamivudine, or stavudine
- •No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: capecitabine (Drug)
Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0
时间窗: 3 weeks
次要结局
- Time to treatment failure(From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months)
- Incidence of UTG1A1*28 polymorphism(Up to 3 months)
- Adverse events profile assessed using NCI CTCAE v3.0(Up to 3 months)
- Toxicity profile assessed using NCI CTCAE v3.0(Up to 3 months)
- Response profile using RECIST criteria(Up to 3 months)
- Time until any treatment related toxicity(Up to 3 months)
- Time until treatment related grade 3+ toxicity(Up to 3 months)
- Time until hematologic nadirs (WBC, ANC, platelets)(Up to 3 months)
- Time to progression(Up to 3 months)