A Phase I Dose-Escalation Trial of Biweekly Intraperitoneal Oxaliplatin With Systemic Capecitabine and Bevacizumab Following Cytoreduction in Patients With Peritoneal Carcinomatosis From Appendiceal or Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after surgical debulking and peritoneal scan documenting functional of intraperitoneal ports in patients with peritoneal carcinomatosis
研究概览
简要总结
This study is to test escalating doses of intraperitoneal (IP) oxaliplatin in conjunction with systemic bevacizumab and capecitabine in patients with Peritoneal Carcinomatosis (PC) from either appendiceal or colorectal adenocarcinoma that have been adequately cytoreduced and have undergone a peritoneal scan demonstrating patency of at least one of the intraperitoneal ports that were placed at the time of debulking.
详细描述
- To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after adequate surgical debulking and peritoneal scan documenting function of intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology.
- To assess the safety and tolerability of repeated delayed intraperitoneal chemotherapy with oxaliplatin and systemic intravenous bevacizumab and oral capecitabine after adequate surgical debulking and peritoneal scan documenting function of intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology.
- To describe the progression rate, progression-free survival and overall survival in patients treated with this regimen.
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
- 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
- •Histological Diagnosis: Patients must have a histologically documented peritoneal carcinomatosis from either colorectal or appendiceal adenocarcinoma.
- •Prior Surgical Debulking: Patients must have undergone debulking surgery with peritonectomy and have been allowed at least 4 weeks to recover prior to receiving chemotherapy.
- •Port Placement: Intraperitoneal ports may be placed during or at any time separate from surgical debulking. Provided the patient has been allowed at least 4 weeks to recover from surgical debulking, no additional recovery time is required for port placement.
- •Active port: Patients must undergo a peritoneal scan documenting at least one working intraperitoneal port prior to receiving chemotherapy.
- •Patients may have received prior chemotherapy.
- •Age: Patients must be ≥18 years of age. Because no dosing or toxicity data are currently available on the use of oxaliplatin in patients <18 years of age.
- •Performance Status: (Eastern cooperativeOncology Group) ECOG 0-
- •Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmias.
- •Informed Consent: All patients must be consented prior to chemotherapy. The patient should not have any serious medical of psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
- •Hematological Status:
- •absolute neutrophil count ≥1,500/mm³
- •platelet count ≥100,000/mm³
- •hemoglobin ≥8 g/dl.
- •Hepatic function:
- •Total bilirubin must be <2X the institutional upper limit of normal (ULN)
- •Transaminases (SGOT and/or SGPT) must be ≤3X the institutional upper limit of normal (ULN)
- •Alkaline phosphatase must be ≤4X the institutional upper limit of normal (ULN)
- •Renal Function: Patients must have adequate renal function prior to chemotherapy defined as serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥60 ml.min/1.73 m² for patients with creatinine levels above 2.0 mg/dl.
排除标准
- •Pregnant or breast feeding: For all sexually active patients, the use of adequate contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry, and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential.
- •Prior history of hypersensitivity reactions to oxaliplatin, bevacizumab, 5-FU or capecitabine.
- •Gastrointestinal ailments that may alter the absorption of oral medications (i.e. bowel obstruction, short-gut syndrome).
- •Patients receiving antiretroviral therapy Highly Active Anti Retroviral Treatment (HAART) for HIV infection are excluded from the study because of possible pharmacokinetic interactions. Appropriate studies will be undertaken in patients receiving HAART therapy, when indicated.
- •Patients with Grade 2 or higher peripheral neuropathy.
研究组 & 干预措施
Dose Level 1
Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Bevacizumab (Drug)
Dose Level 1
Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Capecitabine (Drug)
Dose Level 2
Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Bevacizumab (Drug)
Dose Level 3
Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Capecitabine (Drug)
Dose Level 4
Intraperitoneal oxaliplatin 85 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Bevacizumab (Drug)
Dose Level 2
Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Capecitabine (Drug)
Dose Level 3
Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Bevacizumab (Drug)
Dose Level 3
Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Intraperitoneal Oxaliplatin (Drug)
Dose Level 1
Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Intraperitoneal Oxaliplatin (Drug)
Dose Level 2
Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Intraperitoneal Oxaliplatin (Drug)
Dose Level 5
Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Intraperitoneal Oxaliplatin (Drug)
Dose Level 5
Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Bevacizumab (Drug)
Dose Level 5
Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle
Bevacizumab 5 mg/kg CIVI on day 1 of each cycle
Capecitabine PO BID on days 1-7 of each cycle.
Each cycle is 14 days long.
干预措施: Capecitabine (Drug)
结局指标
主要结局
To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after surgical debulking and peritoneal scan documenting functional of intraperitoneal ports in patients with peritoneal carcinomatosis
时间窗: Completion of enrollment (approximately 8 years)
Progression rate
时间窗: Through 4-12 weeks post-treatment (estimated to be 30 weeks)
-Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions
Assess the safety and tolerability of IP oxaliplatin and intravenous (i.v.) bevacizumab and oral capecitabine after surgical debulking and functional intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology
时间窗: 30 days after completion of treatment (estimated to be 22 weeks)
Overall survival
时间窗: Through completion of follow-up (estimated to be 5 years)
Progression-free survival (PFS)
时间窗: Through completion of follow-up (estimated to be 5 years)
-Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions
次要结局
未报告次要终点