A Phase I/II Study to Evaluate the Efficacy and Toxicity of Imatinib Mesylate in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximum tolerated doses (MTD) for the combination of imatinib mesylate, capecitabine, and dacarbazine
研究概览
简要总结
Objectives:
Primary objectives:
To determine the maximum tolerated doses (MTD) for the combination of imatinib mesylate, capecitabine, and dacarbazine in patients with solid tumors.
To determine the overall tumor response rate to imatinib mesylate in combination with capecitabine and dacarbazine as first line and second line therapy in advanced metastatic medullary thyroid carcinoma.
To determine the tolerability (toxicity) of this regimen.
Secondary objectives:
To determine the median overall survival (OS) and time to progression (TTP) for patients treated with this combination.
详细描述
Phase I:
Imatinib mesylate is a drug that binds to certain proteins on the tumor cells, which may prevent the cells from growing. Capecitabine and dacarbazine are drugs that interfere with the growth of cancer cells.
If you are found to be eligible to take part in this study, you will begin treatment with imatinib mesylate, capecitabine, and dacarbazine.
You will come to M. D. Anderson at least once every three weeks (21 days) for treatment. Each 21-day period of treatment is called a "cycle" of therapy. You will receive at least 3 cycles of therapy (9 weeks) unless side effects are severe or the cancer grows very quickly.
The first group of study participants will receive lower doses of imatinib mesylate, capecitabine and dacarbazine. If these doses appear to be safe, the next group of participants will receive higher doses. This will continue until the highest doses that may be safely given are found.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 16 years old.
- •Signed informed consent.
- •During the phase I portion of the trial, any patient with a proven solid tumor for which no curative or standard treatment is available is eligible. However, for the phase II portion of the trial, patients are required to have medullary thyroid carcinoma that is unresectable or metastatic.
- •For the phase I portion of the protocol, there is no limit to the amount of prior therapy participants may have received. For the phase II portion of the trial, 0-1 prior regimens are allowed.
- •ECOG performance status must be 0-
- •Adequate hepatic, renal, and bone marrow function: Absolute neutrophil count greater than/equal to 1,500/uL; platelets greater than/equal to 100,000/uL; total bilirubin less than/equal to 1.5 X institution upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) less than/equal to 2.5 X institutional ULN; Creatinine less than/equal to 1.5 mg/dL
- •Female patients of childbearing potential must have a negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- •Patients may have received prior radiation treatment but the last fraction of radiation treatment must have been completed at least 4 weeks prior to entry on this study.
- •Patients may have been treated with surgery but the surgical intervention must have been done at least 3 weeks prior to entry on this study.
- •In the phase I part of the trial, measurable disease is not required. Radiographic and measurable evidence of disease is required for the phase II part of the trial. To be considered evaluable for complete or partial response, patients must have at least one measurable lesion as per the modified RECIST Criteria. If radiation was previously received, measurable disease must occur outside the previous radiation field, unless disease progression has been documented.
- •Both men and women and members of all ethnic groups are eligible for this trial.
排除标准
- •In previously treated patients, patients should not have received prior dacarbazine, imatinib mesylate, 5-fluorouracil, or capecitabine. This requirement does not apply to the phase I patients.
- •Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias not well controlled with medication, myocardial infarction within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients who have had chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier.
- •Patients may not be receiving any other investigational agents, or have participated in any investigational drug study within 28 days preceding start of study treatment.
- •The teratogenic potential of this combination is currently unknown. Women who are pregnant or lactating are excluded.
- •History of any other malignancy in the last 5 years, except that patients with a prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with treated disease processes believed to be associated with MEN2, such as pheochromocytomas and primary hyperparathyroidism are allowed in the study.
- •Concomitant use of warfarin is not allowed. Low molecular weight and standard heparin use is allowed.
研究组 & 干预措施
Capecitabine + Dacarbazine + Imatinib
Capecitabine starting Dose 500 mg/m^2 twice a day Days 1-14 of 21 Day Cycle. Dacarbazine starting Dose 250 mg/m^2 a day on Days 1-3 of 21 Day Cycle. Imatinib starting Dose 400 mg a day on Days 1-21 of 21 Day Cycle.
干预措施: Capecitabine (Xeloda) (Drug)
Capecitabine + Dacarbazine + Imatinib
Capecitabine starting Dose 500 mg/m^2 twice a day Days 1-14 of 21 Day Cycle. Dacarbazine starting Dose 250 mg/m^2 a day on Days 1-3 of 21 Day Cycle. Imatinib starting Dose 400 mg a day on Days 1-21 of 21 Day Cycle.
干预措施: DTIC-Dome (Dacarbazine) (Drug)
Capecitabine + Dacarbazine + Imatinib
Capecitabine starting Dose 500 mg/m^2 twice a day Days 1-14 of 21 Day Cycle. Dacarbazine starting Dose 250 mg/m^2 a day on Days 1-3 of 21 Day Cycle. Imatinib starting Dose 400 mg a day on Days 1-21 of 21 Day Cycle.
干预措施: Gleevec (Imatinib Mesylate) (Drug)
结局指标
主要结局
Maximum tolerated doses (MTD) for the combination of imatinib mesylate, capecitabine, and dacarbazine
时间窗: 21 day cycle
The MTD is defined as the dose level below that producing dose limiting toxicity (DLT; i.e. any Grade 4 hematologic toxicity and /or non hematological toxicity \>/= Grade 3 in 2/6 participants).
次要结局
- Objective Response Rate(Minimally 9 weeks (overall study period 5 years))