A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Objective Response Rate Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
研究概览
简要总结
This phase II trial is studying how well giving doxorubicin together with bortezomib works in treating patients with liver cancer. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving doxorubicin together with bortezomib may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the tumor response rate in patients with hepatocellular carcinoma (HCC).
SECONDARY OBJECTIVES:
I. To determine other parameters of antitumor effect including time to tumor progression and overall survival in HCC patients treated with bortezomib and doxorubicin.
II. To observe toxicity profile of bortezomib and doxorubicin in patients with hepatocellular carcinoma.
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
- •Patients must have microscopically confirmed hepatocellular carcinoma not amenable to curative resection; if patients have an isolated lesion in one lobe of the liver, a liver surgeon should determine resectability; central review is not required
- •Patients must have measurable disease as determined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, amenable to biopsy; patients are not mandated to allow biopsy, even though it is an important aspect of this clinical trial
- •Patients with history of malignancy treated within the past 5 years are not eligible; history of carcinoma-in-situ of cervix, squamous cell cancer of skin, basal cell cancer of skin, previously treated are allowed; others are excluded as recurrence of disease may confuse response rate and/or survival endpoints
- •Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Patients must not have had prior systemic chemotherapy for HCC; patients on antineoplastics for non-malignant diseases, such as methotrexate for rheumatoid arthritis, are allowed, providing patients have been off these agents for at least 4 weeks and all related toxicities have resolved to baseline
- •Patients may have had prior embolization without chemotherapy; patients who have had chemoembolization are not eligible; patients may have had radiofrequency (RF) ablation, cryosurgery or ethanol injection; patients must have documented progression with the involved lesion or at least one previously untreated lesion amenable to biopsy
- •Platelet count must be >= 100,000/mm^3 in absence of splenomegaly; platelet count must be >= 75,000/mm^3 with splenomegaly
- •Absolute neutrophil count (ANC) must be >= 1,500/mm^3 in absence of splenomegaly; ANC must be =< 1,000/mm^3 with splenomegaly
- •Alkaline phosphate (ALT) must be =< 5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) must be =< 5 x institutional ULN
- •Bilirubin must be =< 2 mg/dl
- •Patients may not exhibit Child Pugh scale grade C cirrhosis
- •Serum creatinine=< 2.0 mg/dl
- •All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- •Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
- •Patients must not have known bleeding diathesis, international normalized ratio (INR) > 1.5 or Partial thromboplastin time (PTT) > 1.5 x institutional ULN (required due to biopsy portion of study); use of vitamin K or fresh frozen plasma to correct values just prior to biopsy or enrollment is not allowed are not eligible
- •Exclusion criteria:
- •Patients have baseline peripheral neuropathy > grade 1
- •Patients with history of untreated malignancy other than HCC
- •Patients have had prior use of octreotide or tamoxifen as therapy for HCC
- •Patients with known allergy to boron, mannitol or bortezomib
- •Women are pregnant or breast-feeding (due to the uncertain effects of bortezomib in the developing fetus and young infants)
- •Patients have an underlying medical condition that precludes safe participation in this clinical trial
- •Patients have psychiatric illness or continued substance abuse that may impair the ability to provide informed consent or prevent safe administration of bortezomib
- •Patients with ejection fraction (EF) < 50% measured by Echocardiography (ECHO) or Multiple gated acquisition (MUGA)
- •Patients on verapamil who cannot be switched to an alternative medication (due to the interaction with doxorubicin)
排除标准
- 未提供
研究组 & 干预措施
Treatment (doxorubicin+bortezomib)
Patients receive doxorubicin IV over 5-15 minutes on days 1 and 8. Patients also receive bortezomib at a dose of 1.3 mg/m^2 IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no disease progression may continue to receive bortezomib alone in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin (Drug)
Treatment (doxorubicin+bortezomib)
Patients receive doxorubicin IV over 5-15 minutes on days 1 and 8. Patients also receive bortezomib at a dose of 1.3 mg/m^2 IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no disease progression may continue to receive bortezomib alone in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
结局指标
主要结局
Objective Response Rate Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
时间窗: assessed every 3 cycles while on treatment. After discontinuing treatment, assessed every 3 months for 2 years and then every 6 months for 1 year
Tumor response was measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.0. Objective response rate included complete response (disappearance of all tumor lesions) and partial response (At least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.).
次要结局
- Overall Survival(assessed every 3 months for 2 years and then every 6 months for 1 year)
- Progression Free Survival(assessed every 3 cycles while on treatment. After discontinuing treatment, assessed every 3 months for 2 years and then every 6 months for 1 year.)