Phase I Trial of Vorinostat (NSC-701852, Suberoylanilide Hydroxamic Acid) and Doxorubicin (NSC-123127, Adriamycin)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety and tolerability as assessed by NCI CTCAE v3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of vorinostat when given together with doxorubicin in treating patients with metastatic or locally advanced solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help doxorubicin work better by making tumor cells more sensitive to the drug.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of vorinostat (SAHA) and doxorubicin hydrochloride in patients with metastatic or locally advanced solid tumors.
II. Determine the maximum tolerated dose of vorinostat when administered with doxorubicin hydrochloride in patients treated with this regimen.
SECONDARY OBJECTIVES:
I. Determine the response rate (complete response [CR] and partial response [PR]) and clinical benefits rate (CR, PR, and stable disease > 12 weeks) in patients treated with this regimen.
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 solid tumor malignancies for which no curative therapy exists
- •Measurable or evaluable disease with tumor that is accessible to biopsy as determined by CT scan or ultrasound
- •Skin, lymph nodes, or chest wall lesions are allowed provided measurements are confirmed by 2 independent health care professionals
- •No uncontrolled CNS metastases
- •Patients with stable CNS metastases (either surgically resected, treated with gamma knife, or stable for 3 months after whole-brain radiotherapy and documented by MRI within the past 4 weeks) are eligible
- •Willing to undergo pre- and post-vorinostat tumor biopsies
- •Life expectancy ≥ 3 months
- •ECOG performance status 0-2
- •WBC > 3,000/mm^3
- •Absolute neutrophil count > 1,500/mm^3
- •Hemoglobin > 9.0 g/dL
- •Platelet count > 100,000/mm^3 (transfusion independent)
- •Creatinine ≤ 2.0 mg/mL
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 1.5 times ULN
- •LVEF > 50%
- •Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- •Negative pregnancy test
- •Not pregnant or nursing
- •No significant active infection (e.g., pneumonia, cellulitis, or wound abscess)
- •No history of cardiac failure
- •No history of long QT syndrome (QTc > 470 msec)
- •No history of ventricular tachycardia or fibrillation
- •No history of seizures
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat or other agents used in the study
- •More than 3 weeks since prior chemotherapy or radiotherapy (2 weeks for weekly regimens)
- •More than 2 weeks since prior valproic acid or any other histone deacetylase inhibitors
- •No prior anthracycline exposure
- •No other concurrent chemotherapy
- •No concurrent hormonal therapy except for maintenance therapy with luteinizing-hormone releasing-hormone agonists
- •No concurrent antiarrhythmics
- •No concurrent steroids to control brain metastasis
- •No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study treatment
- •No other concurrent investigational agents for primary disease
排除标准
- 未提供
研究组 & 干预措施
Treatment (vorinostat, doxorubicin hydrochloride)
Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.
干预措施: doxorubicin hydrochloride (Drug)
Treatment (vorinostat, doxorubicin hydrochloride)
Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.
干预措施: vorinostat (Drug)
Treatment (vorinostat, doxorubicin hydrochloride)
Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.
干预措施: pharmacological study (Other)
Treatment (vorinostat, doxorubicin hydrochloride)
Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Safety and tolerability as assessed by NCI CTCAE v3.0
时间窗: Up to 30 days after completion of treatment
Maximum tolerated dose (MTD) of vorinostat as assessed by NCI CTCAE v3.0
时间窗: 28 days
次要结局
- Response rate (CR and PR) and clinical benefits rate (CR, PR, and stable disease) according to RECIST(Up to 30 days after completion of study treatment)
- Duration of response (overall response, complete response, and stable disease)(Up to 30 days after completion of study treatment)
- Correlation of dose and response with biological markers for histone acetylation, Topo II expression, assays for comet moments and expression patterns of chromatin structural proteins dose(Up to 30 days after completion of study treatment)
- Effects of vorinostat on histone acetylation(At baseline and at day 3 prior)