A Multi-arm Phase I Trial of Hepatic Arterial Infusion of Irinotecan With 1) Systemic Bevacizumab 2) Systemic Bevacizumab and Oxaliplatin 3) Systemic Bevacizumab and Cetuximab in Patients With Advanced Cancers Metastatic to the Liver
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Doses (MTDs)
研究概览
简要总结
The goal of this clinical research study is to learn the highest tolerable dose of irinotecan that can be given directly into the liver, in combination with other drugs given by vein.
The other drug combinations given by vein include bevacizumab alone, bevacizumab plus oxaliplatin, and bevacizumab plus cetuximab.
This will be tested in patients with advanced solid tumors that have spread to the liver. The safety of these drug combinations will also be studied.
详细描述
The Study Drugs:
Irinotecan is designed to stop cancer cells from making new DNA (the genetic material of cells). This may cause cancer cells to die.
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients necessary for tumor growth.
Oxaliplatin is designed to block new cancer cells from growing.
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside cancer cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed metastatic advanced cancers with liver involvement.
- •Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months, unless the drugs included in the regimen are part of their standard treatment.
- •Irinotecan will be dosed regardless of creatinine clearance. For oxaliplatin, serum creatinine </= 2.5 times the upper limit of normal or creatinine clearance >/= 40 is required.
- •Hepatic function: T. Bilirubin </= 3 mg/dl, ALT </= 5X upper limit of normal (ULN).
- •Adequate bone marrow function (ANC >/=1000 cells/uL; PLT >/= 100,000 cells/uL).
- •Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available.
- •All females in childbearing age MUST have a negative serum or urine pregnancy test 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.
- •Eastern Cooperative Oncology Group (ECOG) Performance status </= 2.
排除标准
- •Pregnant females.
- •Patients with colorectal cancer and K-RAS mutation will be excluded from the cetuximab arm.
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- •Invasive procedures defined as follows: a. Major surgical procedure within 28 days prior to Day 1 therapy. b. Anticipation of need for major surgical procedures during the course of the study.
- •Patients receiving any other investigational agents.
- •Patients with bleeding diathesis (clinical bleeding, prothrombin time >/= 1.5 X upper institutional normal value, international normalized ratio (INR) >/=1.5, activated partial thromboplastin time aPTT >/= 1.5 X upper institutional normal value, NOT due to anticoagulation therapy), active gastric or duodenal ulcer.
- •Patients with history of bleeding CNS metastasis will be excluded from the trial.
- •Hypersensitivity to any of the drugs in a particular treatment arm.
- •Inability to complete informed consent process and adhere to protocol treatment plan and follow up requirements.
- •History of heparin-induced thrombocytopenia.
- •Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
研究组 & 干预措施
Group 1
Group 1 = Irinotecan + Bevacizumab
干预措施: Irinotecan (Drug)
Group 1
Group 1 = Irinotecan + Bevacizumab
干预措施: Bevacizumab (Drug)
Group 2
Group 2 = Irinotecan, Bevacizumab + Oxaliplatin
干预措施: Irinotecan (Drug)
Group 2
Group 2 = Irinotecan, Bevacizumab + Oxaliplatin
干预措施: Bevacizumab (Drug)
Group 2
Group 2 = Irinotecan, Bevacizumab + Oxaliplatin
干预措施: Oxaliplatin (Drug)
Group 3
Group 3 = Irinotecan, Bevacizumab + Cetuximab
干预措施: Irinotecan (Drug)
Group 3
Group 3 = Irinotecan, Bevacizumab + Cetuximab
干预措施: Bevacizumab (Drug)
Group 3
Group 3 = Irinotecan, Bevacizumab + Cetuximab
干预措施: Cetuximab (Drug)
结局指标
主要结局
Maximum Tolerated Doses (MTDs)
时间窗: Evaulated with each 28 day cycle
MTD is defined as the highest dose level at which ≥ 33% of patients have a DLT if \>3 patients are treated at that dose level or \> 33% have a DLT if ≤3 patients have been treated.
Dose-limiting toxicities (DLTs)
时间窗: Evaulated with each 28 day cycle
DLT defined as any grade 3 or 4 non-hematologic toxicity defined in NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; 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; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.
次要结局
未报告次要终点