A Phase II Trial Of Gemcitabine And Triapine In Refractory Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Confirmed response (complete or partial response)
研究概览
简要总结
Phase II trial to study the effectiveness of combining 3-AP with gemcitabine in treating patients who have refractory metastatic breast cancer. Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 3-AP with gemcitabine may kill more tumor cells
详细描述
OBJECTIVES: Primary I. Determine antitumor activity of 3-AP (Triapine®) and gemcitabine by measuring tumor size in patients with refractory metastatic breast cancer.
Secondary I. Determine the safety and tolerability of this regimen in these patients. II. Determine the time to disease progression in patients treated with this regimen.
III. Determine the effect of multidrug resistance polymorphisms on pharmacokinetics and toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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 breast cancer
- •Refractory metastatic disease
- •Measurable disease
- •At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- •Must have received 1, and only 1, prior chemotherapy regimen for metastatic disease
- •Patients overexpressing HER2/neu antigen must have received a prior trastuzumab (Herceptin®)-containing regimen
- •No known brain metastases
- •Hormone receptor status:
- •Not specified
- •Male or female
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal
- •Creatinine clearance ≥ 60 mL/min
- •No uncontrolled congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No severe pulmonary disease requiring oxygen
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •No other uncontrolled illness
- •No active or ongoing infection
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to 3-AP (Triapine®) or other study agents
- •No psychiatric illness or social situation that would preclude study compliance
- •No other malignancy within the past 5 years
- •See Disease Characteristics
- •No concurrent immunotherapy
- •No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
- •See Disease Characteristics
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •No prior gemcitabine for metastatic disease
- •No other concurrent chemotherapy
- •More than 4 weeks since prior hormonal therapy
- •More than 4 weeks since prior radiotherapy
- •No concurrent radiotherapy
- •Recovered from prior therapy
- •No concurrent antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational therapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (triapine, gemcitabine hydrochloride)
Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: triapine (Drug)
Treatment (triapine, gemcitabine hydrochloride)
Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: gemcitabine hydrochloride (Drug)
Treatment (triapine, gemcitabine hydrochloride)
Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (triapine, gemcitabine hydrochloride)
Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Confirmed response (complete or partial response)
时间窗: Up to 6 months
Ninety five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
次要结局
- Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0(Up to 3 years)
- Time to progression(Time from registration to the time of progression, assessed up to 3 years)
- Overall survival(Time from registration to death due to any cause, assessed up to 3 years)
- Changes in tyrosyl radical and cell-cycle arrest on buccal mucosa(Pre-infusion, 2 and 4.5 hours post-infusion)
- Changes in R2 messenger ribonucleic acid (mRNA) on protein levels before and after treatment with triapine(Pre-infusion, 2 and 4.5 hours post-infusion)
- MDR polymorphism on tumor tissue(Baseline)