Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Bevacizumab With/Without Cetuximab by K-RAS Mutational Status and Liver Function for Advanced Cancers Metastatic to the Liver
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Anti-Tumor Efficacy
研究概览
简要总结
The goal of this clinical research study is to find the best combination of oxaliplatin, bevacizumab, 5-fluorouracil, leucovorin, and cetuximab that can be given to patients with advanced cancer that has spread to the liver. Different combinations of these drugs will be used, and the safety of all drug combinations will also be studied.
详细描述
The Study Drugs:
Oxaliplatin is designed to keep new cancer cells from growing.
5-fluorouracil is designed to block the way cancer cells grow and divide, which may slow or stop their growth and keep them from spreading throughout the body. This may cause the cancer cells to die.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to 5-fluorouracil. BECAUSE OF A PHARMACY SHORTAGE OF IV LEUCOVORIN, PATIENTS WILL CONTINUE TREATMENT WITHOUT LEUCOVORIN UNTIL IT BECOMES AVAILABLE.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 must have histologically confirmed cancer with metastatic liver metastases.
- •Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months, unless the drugs in the protocol regimen are part of the standard of care.
- •Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (Capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
- •Adequate renal function (Serum Creatinine </= 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
- •Patients will be stratified by liver function tests: Normal liver function: Total Bilirubin </= 3 mg/dL, Alanine aminotransferase (ALT) </= 5 times upper normal reference value. Abnormal liver function: Total bilirubin >3 mg/dL and/or elevated ALT > 5 x upper limit of normal (ULN). If bilirubin is >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted. Both of the above groups will be eligible.
- •Adequate bone marrow function (Absolute Neutrophil Count (ANC) >/=1500 cells/uL; Platelets (PLT) >/= 100,000 cells/uL).
- •At least three weeks from previous cytotoxic chemotherapy before day 1 of hepatic arterial infusion (HAI) infusion. After targeted or biologic therapy, there should be 5 half-lives or three weeks, whichever is shorter.
- •All females in childbearing age MUST have a negative urine human chorionic gonadotropin (HCG) 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.
- •Ability to sign informed consent form. Pediatric: age 7-18 would sign assent, (<7 would not assent), parent or guardian would sign consent.
- •Patients with colorectal cancer must agree to K-RAS mutational status screening, if not available. If tissue is not available, patients can enter on trial, but not on the cetuximab arms.
排除标准
- •Pregnant females.
- •Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- •Serious or non-healing wound, ulcer or bone fracture.
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- •Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
- •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).
研究组 & 干预措施
Group 1
HAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab
干预措施: HAI Oxaliplatin (Drug)
Group 1
HAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab
干预措施: 5-FU (Drug)
Group 1
HAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab
干预措施: Bevacizumab (Drug)
Group 2
HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
干预措施: HAI Oxaliplatin (Drug)
Group 2
HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
干预措施: Bevacizumab (Drug)
Group 2
HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
干预措施: Leucovorin (Drug)
Group 2
HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab
干预措施: 5-FU (Drug)
Group 3
HAI oxaliplatin in combination with IV bevacizumab.
干预措施: HAI Oxaliplatin (Drug)
Group 3
HAI oxaliplatin in combination with IV bevacizumab.
干预措施: Bevacizumab (Drug)
Group 4
HAI oxaliplatin in combination with IV bevacizumab and cetuximab.
干预措施: HAI Oxaliplatin (Drug)
Group 4
HAI oxaliplatin in combination with IV bevacizumab and cetuximab.
干预措施: Cetuximab (Drug)
Group 4
HAI oxaliplatin in combination with IV bevacizumab and cetuximab.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Anti-Tumor Efficacy
时间窗: After 2, 21 day cycles
Response Evaluation Criteria in Solid Tumors (RECIST) guidelines used to assess the efficacy of this regimen. A 20% increase in the sum of the greatest longitudinal diameters considered stable disease in the absence of clinical symptoms. An exploratory analysis of radiographic tool measuring the diameter of tumor lesions and comparing their tissue density in comparison with liver function studies and serum biochemical markers performed among study participants.
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin
时间窗: 21 days
If more than 33% of patients enrolled in any particular dose level develop DLT, the treatment will continue at the dose level immediately below. If not more than 33% of the patients in the cohort develop DLT, this cohort will be considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v3.0, any Grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI CTC), despite supportive care or associated with bleeding and/or sepsis; 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; or any severe or life-threatening complication or abnormality not covered in the NCI CTC. The MTD defined by DLTs that occur in the first cycle.
次要结局
未报告次要终点