A Phase I Clinical Trial of Hepatic Arterial Infusion of Oxaliplatin, Oral Capecitabine, With or Without Systemic Bevacizumab for Patients With Advanced Cancer Metastatic to the Liver
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Hepatic Arterial IUnfusion (HAI) Oxaliplatin, with Oral Capecitabine, with or without Systemic Intravenous Bevacizumab
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of oxaliplatin and capecitabine with or without bevacizumab that can be given to patients with advanced cancer that has spread to the liver. The safety of these drug combinations will also be studied.
详细描述
The Study Drugs:
Oxaliplatin is designed to keep new cancer cells from growing.
Capecitabine is designed to interfere with the growth of cancer cells.
Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Study Groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 histologically confirmed cancer with predominant liver metastases.
- •Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (capable of all self care but unable to carry out any work activities).
- •Adequate renal function (creatinine clearance >50 mL/min).
- •Adequate liver function: total bilirubin </= 4 mg/dL, alanine transaminase (ALT) </= 5 times upper normal reference value. Patients with total bilirubin between 3.0 and 4.0 mg/dL must have blood ammonia level checked at baseline. Blood ammonia level must be within normal limits for enrollment.
- •Adequate bone marrow function (absolute neutrophil count (ANC) >/= 1000 cells/uL; platelets (PLT) >/= 70,000 cells/uL).
- •At least 3 weeks from prior cytotoxic chemotherapy or radiation therapy. If targeted or biologic therapy, there should be at least 5 half lives or 3 weeks, whichever is shorter, from day 1 of treatment.
- •All females in childbearing age MUST have a negative urine human chorionic gonadotropin (HCG) test before the first dose, unless prior hysterectomy or menopause (defined as age above 55 and six months without menstrual activity). Patients should not become pregnant or breast-feed while on this study. Sexually active patients should use effective birth control.
- •Ability and willingness to sign informed consent form.
- •Must be >/= 18 years of age.
- •Patients with unresectable liver-only (isolated liver) metastases are eligible; those who show adequate response may be considered for liver resection and/or radiofrequency ablation (RFA) of remaining disease.
排除标准
- •Pregnant females.
- •Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- •Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients already in uncompensated liver failure (i.e., Child Pugh Liver Classification C).
- •History of hypersensitivity to any component of the formulation.
- •Exclusion criteria only for patients enrolled in Arm 1: Serious or non-healing wound, ulcer, or bone fracture.
- •Exclusion criteria only for patients enrolled in Arm 1: Any history of abdominal fistula or gastrointestinal perforation; or intra-abdominal abscess within 28 days of enrollment.
- •Exclusion criteria only for patients enrolled in Arm 1: Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic Blood Pressure > 90 mm Hg).
- •Exclusion criteria only for patients enrolled in Arm 1: History of bleeding CNS metastases.
研究组 & 干预措施
Oxaliplatin + Capecitabine + Bevacizumab
Oxaliplatin 140 mg/m2 by Hepatic Arterial Catheter (HAI) on day 1 of a 21 day cycle. Capecitabine starting dose of 500 mg/m2 by mouth twice daily, on days 1 - 14 of a 21 day cycle. Bevacizumab 10 mg/kg by vein on day 1 of a 21 day cycle.
干预措施: Oxaliplatin (Drug)
Oxaliplatin + Capecitabine + Bevacizumab
Oxaliplatin 140 mg/m2 by Hepatic Arterial Catheter (HAI) on day 1 of a 21 day cycle. Capecitabine starting dose of 500 mg/m2 by mouth twice daily, on days 1 - 14 of a 21 day cycle. Bevacizumab 10 mg/kg by vein on day 1 of a 21 day cycle.
干预措施: Capecitabine (Drug)
Oxaliplatin + Capecitabine + Bevacizumab
Oxaliplatin 140 mg/m2 by Hepatic Arterial Catheter (HAI) on day 1 of a 21 day cycle. Capecitabine starting dose of 500 mg/m2 by mouth twice daily, on days 1 - 14 of a 21 day cycle. Bevacizumab 10 mg/kg by vein on day 1 of a 21 day cycle.
干预措施: Bevacizumab (Drug)
Oxaliplatin + Capecitabine
Oxaliplatin 140 mg/m2 by Hepatic Arterial Catheter (HAI) on day 1 of a 21 day cycle. Capecitabine starting dose of 500 mg/m2 by mouth twice daily, on days 1 -14 of a 21 day cycle.
干预措施: Oxaliplatin (Drug)
Oxaliplatin + Capecitabine
Oxaliplatin 140 mg/m2 by Hepatic Arterial Catheter (HAI) on day 1 of a 21 day cycle. Capecitabine starting dose of 500 mg/m2 by mouth twice daily, on days 1 -14 of a 21 day cycle.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Hepatic Arterial IUnfusion (HAI) Oxaliplatin, with Oral Capecitabine, with or without Systemic Intravenous Bevacizumab
时间窗: First 21 day cycle
If more than 33% of patients enrolled in any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of the patients in cohort develop DLT, this cohort considered MTD. DLT defined as any grade 3 or 4 non-hematologic toxicity as defined in current version of NCI CTCAE, even if related to study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; grade 4 thrombocytopenia; any grade 4 neutropenia of more than seven days duration, despite supportive care or associated with bleeding and/or sepsis; or any severe or life-threatening complication or abnormality not covered in NCI CTCAE. MTD defined by DLTs that occur in first cycle.
次要结局
未报告次要终点