A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients With Advanced Solid Tumors Metastatic to the Liver
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver.
研究概览
简要总结
PRIMARY:
- To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver.
SECONDARY:
- To document in a descriptive fashion the antitumor efficacy of this combination regimen.
- To evaluate the feasibility and accuracy of an alternate radiographic assessment tool and compare with available tumor markers and RECIST guidelines.
- To estimate in a descriptive fashion the development of extrahepatic tumor recurrences.
详细描述
Oxaliplatin is designed to interfere with the growth of cancer cells (which slows their growth and spreading), eventually destroying them.
5-fluorouracil is designed to interfere with the growth of cells that reproduce rapidly.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to the 5-fluorouracil.
Bevacizumab is designed to interfere with blood flow to your tumors, which may cause tumors to be "starved" of the oxygen and nutrients they need to grow.
Before you can start on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded and a physical exam, including measurement of your vital signs (blood pressure, temperature, breathing rate, and heart rate). You will have a neurological evaluation (a test to evaluate your strength and nerve functioning). You will have blood drawn (about 1 teaspoon or less) and urine collected for routine tests. Women who are able to have children must have a negative urine pregnancy test.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed metastatic advanced solid tumors involving the liver.
- •Pediatric patients eligible at the discretion of the primary investigator.
- •Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any work activities).
- •Adequate renal function (Serum Creatinine </= 2.0 mg/dL) or a calculated creatinine clearance greater than 60 mL/min.
- •Hepatic function as follows: In treatment arm 1: Total Bilirubin </= 3 mg/dL, AST </= 5 times upper normal reference value, or ALT </= 5 times upper normal reference value). In treatment arm 2: Total bilirubin >3 mg/dL. If bilirubin >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted.
- •Adequate bone marrow function (ANC >/=1500 cells/uL; PLT >/= 100,000 cells/uL).
- •At least three weeks from previous immunotherapy, chemotherapy or radiotherapy before day of HAI infusion and recovery from any associated toxicities to less or equal to Grade
- •All females in childbearing age MUST have a negative serum 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 fully read, comprehend, and sign informed consent forms.
排除标准
- •Clinical or radiographic evidence of ascites.
- •Pregnant females.
- •Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- •Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function but not interfering with ADL)
- •Serious or non-healing wound, ulcer or bone fracture.
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- •Invasive procedures defined as follows; Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy, Anticipation of need for major surgical procedures during the course of the study, Core biopsy within 7 days prior to D1 of therapy.
- •Patients receiving any other investigational agents.
- •Patients with bleeding diathesis (clinical bleeding, prothrombin time =/> 1.5 X upper institutional normal value, INR =/> 1.5, activated partial thromboplastin time aPTT =/> 1.5 X upper institutional normal value), active gastric or duodenal ulcer.
- •Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
- •Urine protein should be screened by dipstick or urine analysis. For proteinuria > 1+ or urine protein:creatinine ratio > 1.0, a 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with clinically significant cardiovascular disease: History of CVA within 6 months, myocardial infarction or unstable angina within 6 months, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris, clinically significant peripheral vascular disease
- •Patients with history of bleeding CNS metastasis will be excluded from the trial.
研究组 & 干预措施
Oxaliplatin + Fluorouracil + Leucovorin + Avastin
干预措施: Fluorouracil (Drug)
Oxaliplatin + Fluorouracil + Leucovorin + Avastin
干预措施: Avastin (Drug)
Oxaliplatin + Fluorouracil + Leucovorin + Avastin
干预措施: Leucovorin (Drug)
Oxaliplatin + Fluorouracil + Leucovorin + Avastin
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver.
时间窗: 5 Years
次要结局
未报告次要终点