Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery
A Phase I Clinical Trial of Oral Calcitriol With Fixed Dose of Cisplatin and Gemcitabine in Patients With Advanced Solid Tumors
研究概览
详细说明
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of oral calcitriol when combined with a standard dose of gemcitabine (gemcitabine hydrochloride) and cisplatin in a 28-day cycle.
SECONDARY OBJECTIVES:
I. Describe the toxicity of this combination using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
II. Study the pharmacokinetics of calcitriol at the maximum tolerated dose (MTD) in an expanded cohort of 6 patients.
III. Describe the clinical activity associated with this regimen in this advanced solid tumor population.
OUTLINE:
Patients receive calcitriol orally (PO) on days 1, 2, 8, 9, 15 and 16; cisplatin intravenously (IV) over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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New York
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Buffalo、New York、美国、14263
- Roswell Park Cancer Institute
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Virginia
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Charlottesville、Virginia、美国、22903
- Emily Couric Clinical Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Patients with a diagnosis of advanced unresectable non-hematological malignancy that has no known standard of care or for which the use of gemcitabine plus cisplatin constitutes a reasonable option
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- White blood cell (WBC) >= 3.0 x 10^9/L
- Neutrophils >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Hemoglobin (Hgb) >= 10 g/dL
- Bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x institutional ULN unless metastatic to liver in which case AST and ALT should be < 5 x institutional ULN
- Creatinine =< 1.5 x institutional ULN
- Corrected calcium =< institutional ULN (corrected calcium = (4- Albumin) x 0.8 + calcium)
- Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
- Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- No treatment with investigational agents within 4 weeks prior to study drug administration, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
- No chemotherapy within 4 weeks prior to study treatment administration; nitrosoureas and mitomycin C are not allowed within 6 weeks prior to initiation of study treatment
- Palliative radiation, including whole brain radiation therapy (WBRT), is allowed prior to enrollment as long as it is completed > 2 weeks from initiation of study treatment, and provided patient has recovered from treatment toxicities to =< grade 1
- Patients should be able to take oral medications
Exclusion Criteria:
- Known hypersensitivity to any of the study drugs involved
- Brain metastases are excluded unless treated and shown to be controlled more than 1 month from after craniotomy or more than 2 weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
- History of clinically significant hypercalcemia
- Evidence of nephrectomy
- History of (within 24 months prior to enrollment) of kidney, ureter, or bladder stones with clinically significant sequelae (e.g. (painless gross hematuria; pain with or without infection; hydronephrosis, etc); patients with otherwise stable non-occluding kidney stones regardless of stone type incidentally found in computed tomography (CT) scans are eligible; patients with prior history of uric acid stones are eligible regardless of time of onset
- Unwillingness to stop calcium supplementation (during the first cycle of treatment) or vitamin D supplementation throughout the study
- Thiazide (e.g HCTZ, Hydrochoirthiazide) or digoxin therapy (e.g Lanoxicaps, Lanoxin)
- Pregnant or nursing female patients.
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug
- Received an investigational agent within 4 weeks prior to enrollment, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
- Nut allergy
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)
Patients receive calcitriol PO on days 1, 2, 8, 9, 15 and 16; cisplatin IV over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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相关研究
其他名称:
鉴于IV
鉴于IV
其他名称:
给定采购订单
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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MTD of oral calcitriol when combined with a standard dose of gemcitabine hydrochloride and cisplatin, determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0
大体时间:28 days
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A standard 3+3 with de-escalation will be used to estimate the MTD.
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28 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Toxicity of this combination, graded according to NCI CTCAE version 4.0
大体时间:Up to 30 days after last dose of study drug
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Tabulated overall or by dose level (as appropriate).
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Up to 30 days after last dose of study drug
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Pharmacokinetic (PK) analyses of calcitriol at the MTD in an expanded cohort of 6 patients, including peak levels, area under the concentration-time curve from time 0-72 hours, terminal half-life, volume of distribution, and total body clearance
大体时间:Days 1-3 of course 1
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PK data will be presented as plots of serum calcitriol concentration over time for each patient.
An assessment of whether systemic calcitriol exposure associated with antitumor activity in preclinical models is achieved in these patients will be made.
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Days 1-3 of course 1
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Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1
大体时间:Up to 5 years
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Responses tabulated as appropriate.
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Up to 5 years
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合作者和调查者
调查人员
- 首席研究员:Grace Dy、Roswell Park Cancer Institute
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
成人实体瘤的临床试验
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Hospital Clinic of BarcelonaUniversitat Politècnica de Catalunya; Institut Catala de Salut; Department of Health, Generalitat... 和其他合作者未知