Phase II Trial of PS-341 (NSC 681239) Followed by the Addition of Doxorubicin at Progression in Advanced Adenoid Cystic Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
研究概览
简要总结
This phase II trial is studying how well bortezomib followed by doxorubicin at the time of disease progression works in treating patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (cancer) of the head and neck. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with doxorubicin may kill more tumor cells
详细描述
OBJECTIVES: Primary I. Determine the objective tumor response in patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck treated with bortezomib.
Secondary I. Determine the time to progression in patients treated with this drug. II. Determine the overall survival of patients treated with this drug. III. Determine the toxic effects of this drug in these patients. IV. Determine the objective tumor response, time to progression, and overall survival of patients who progress on single-agent bortezomib and are then treated with doxorubicin and bortezomib.
V. Determine the toxic effects of this regimen in these patients. VI. Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.
VII. Correlate the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway (NF-kB, p53, p27, cyclin D1, cyclin E, vascular endothelial growth factor [VEGF], MVD, V-CAM, and N-CAM) on tumor tissue with the clinical activity of bortezomib in these patients.
OUTLINE: This is a multicenter study.
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 adenoid cystic carcinoma of the head and neck
- •Locally advanced, recurrent, or metastatic disease that is considered incurable by known therapies
- •Unidimensionally measurable disease
- •Must not have stable disease for at least 9 months before study entry
- •No known brain metastases
- •Performance status - ECOG 0-2
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •AST and ALT no greater than 2.5 times upper limit of normal
- •Bilirubin normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •LVEF at least lower limit of normal by MUGA
- •No history of congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •No active or ongoing infection
- •No prior allergy to compounds of similar chemical or biological composition to bortezomib
- •No other concurrent uncontrolled illness
- •No psychiatric illness or social situation that would preclude study compliance
- •No pre-existing neuropathy > grade 1
- •No other invasive malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- •See Chemotherapy
- •No prior anthracyclines, including any of the following:
- •Doxorubicin
- •Epirubicin
- •Daunorubicin
- •Idarubicin
- •No prior mitoxantrone
- •No prior high-dose chemotherapy for bone marrow transplantation
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •At least 3 weeks since prior radiotherapy
- •At least 3 weeks since prior surgery
- •More than 4 weeks since prior investigational drugs
- •No other concurrent anticancer therapy or agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (bortezomib, doxorubicin hydrochloride)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (bortezomib, doxorubicin hydrochloride)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Treatment (bortezomib, doxorubicin hydrochloride)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Up to 10 years
次要结局
- Toxicities, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0(Up to 30 days after last dose of study treatment)
- Progression free survival(Time from randomization or registration to the earlier of disease recurrence or death from any cause, assessed up to 10 years)
- Overall survival(Time from randomization or registration to date of death (from any cause) or date of last contact, assessed up to 10 years)
- Association of change in cytokine concentration with response to bortezomib therapy(Up to 1 hour post-treatment (course 2))
- Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity(Baseline)