Pilot Trial of Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin
试验速览
- 阶段
- 1 期
- 入组人数
- 46
- 试验地点
- 5
- 主要终点
- Systemic Exposure to Paclitaxel and Carboplatin
研究概览
简要总结
The goal of this clinical research study is to learn about the safety and tolerability of paclitaxel and carboplatin when given in combination with Avastin to patients with ovarian, primary peritoneal, or fallopian tube cancer.
Objectives:
Primary study goals:
To investigate the safety and tolerability of carboplatin and paclitaxel administered IP in combination with IV Avastin To determine if Avastin influences the pharmacokinetics of IP administered chemotherapeutic agents
Secondary study goals:
To determine the systemic exposure to paclitaxel and carboplatin during initial and late cycles of IP dosing.
To collect overall survival (OS) and progression-free survival (PFS) To determine changes in IP VEGF levels To determine site of first recurrence Information on CA-125 response and clinical response will be descriptive as secondary goals of this study
Exploratory goal:
To estimate proportion of patients completing entire course of treatment
详细描述
The Study Drugs:
Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.
Paclitaxel is designed to block the mechanisms of cell division in cancer cells, which may cause them to die.
Avastin is designed to prevent or slow down the growth of cancer cells by blocking the effects of VEGF, a blood-vessel stimulating agent that plays an important role in the growth of both normal and abnormal blood vessels.
Intraperitoneal Port (IP) Placement:
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
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed epithelial carcinoma of mullerian origin. Specifically, ovarian, primary peritoneal and tubal carcinoma will be allowed. All histologic subtypes are eligible.
- •Stage III or IV disease. Stage IV disease by virtue of pleural effusions is allowed but stage IV disease with visceral metastases e.g. lung, liver or abdominal wall is NOT ELIGIBLE. Please discuss any eligibility concerns directly with the P.I., Dr. Richard Penson.
- •Patient must have undergone surgical staging and debulking with optimal (less than 1cm) cytoreduction.
- •No significant intra-abdominal adhesions or other contraindication to IP port placement.
- •Patients must give written informed consent.
- •Patient must be age 18 years or older.
- •Adequate bone marrow function with an ANC greater that 2,500 and Platelets greater than 100,000 cubic millimeters.
- •No proteinuria or less than +1; if greater, 24-hour urine collection must be performed to document less than or equal to 1gm/24 hours of protein.
- •ECOG performance status less than or equal to 1.
排除标准
- •Visible disease on post-operative imaging (recognizing the limitations of postoperative CT scans due to postoperative changes there should be unequivocal CT evidence of residual disease greater than 1cm)
- •ECOG performance status greater than or equal to 2
- •Previous chemotherapy for the disease under study
- •Suboptimal (greater than 1 cm residual disease) cytoreduction
- •Creatinine greater than 1.5 mg/dL
- •SGOT greater than 2 x ULN, bilirubin greater than 1.5 x ULN
- •Colostomy or ileostomy
- •Concurrent invasive malignancy. (Patients with concurrent superficial endometrial carcinoma are eligible if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium.)
- •Known hypersensitivity to E.coli derived products or to any component of Avastin
- •Active psychiatric or mental illness that makes informed consent or careful clinical follow-up unlikely
- •History of myocardial infarction within 6 months
- •History of stroke or transient ischemia attack within 6 months
- •Inadequately controlled hypertension greater than 140/90 mm Hg on antihypertensive medication(s)
- •Any prior history of hypertensive crisis or hypertensive encephalopathy
- •Clinically significant peripheral vascular disease
- •Significant vascular disease (e.g. aortic aneurysm, aortic dissection)
- •Unstable angina
- •New York Heart Association (NYHA) grade II or greater congestive heart failure
- •Evidence of coagulopathy or bleeding diathesis
- •Known central nervous system disease or brain metastases
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 28 (first dose of Avastin), anticipation of need for major surgical procedure during the course of the study
- •Minor surgical procedures such as fine needle aspirations or core biopsies or laparoscopy for IP catheter placement within 7 days prior to cycle 2 day 8
- •Open wound, ulcer, or bone fracture
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess; current signs and symptoms of bowel obstruction; current dependency on IV hydration or TPN
- •Pregnant (positive pregnancy test) or lactating
研究组 & 干预措施
Paclitaxel + Carboplatin + Avastin
Paclitaxel Cycle 1 = 60 mg/m^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m^2 IP weekly over 1 hour x 3 weeks of each cycle.
Carboplatin Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle.
Avastin Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.
干预措施: Paclitaxel (Drug)
Paclitaxel + Carboplatin + Avastin
Paclitaxel Cycle 1 = 60 mg/m^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m^2 IP weekly over 1 hour x 3 weeks of each cycle.
Carboplatin Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle.
Avastin Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.
干预措施: Carboplatin (Drug)
Paclitaxel + Carboplatin + Avastin
Paclitaxel Cycle 1 = 60 mg/m^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m^2 IP weekly over 1 hour x 3 weeks of each cycle.
Carboplatin Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle.
Avastin Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.
干预措施: Avastin (Drug)
结局指标
主要结局
Systemic Exposure to Paclitaxel and Carboplatin
时间窗: Second and fourth 21 day cycle
Primary objective of pharmacokinetic studies is to determine whether rate and extent absorption of paclitaxel and carboplatin into systemic circulation when given by the intraperitoneal port (IP) route is influenced by concurrent administration of Avastin by vein. Sampling to define plasma concentration time courses of paclitaxel and carboplatin performed during second cycle without Avastin and fourth cycle of therapy with Avastin. Pharmacokinetic parameters and variables calculated according to standard equations. Concentration-time profiles of carboplatin and its metabolites analyzed by noncompartmental methods and/or nonlinear least squares regression. Mean values of pharmacokinetic parameters statistically compared using the two-tailed t-test.
Number of Patients Who Complete Entire Treatment Course
时间窗: Total treatment course = 6 cycles (1 cycle is 21 days)
Rate of completers estimated along with a 95% confidence interval to evaluate the tolerability of this regimen.
次要结局
- Median Overall Survival(From the start of treatment until the time of death, up to 20 years)
- Median Progression Free Survival(From the start of treatment until the time of death or progression, up to 10 years)
- Change in Intraperitoneal VEGF levels(Cycle 4-6 day 8, day 1 of cycles 7-12 and 16-18 (cycle is 21 days))
- Site of Cancer First Recurrence(At the time of first recurrence, assessed up to 10 years)
- Change in Plasma CA-125 Level(1 Year)
- Clinical Response Rate(1 Year)
研究者
Richard Thomas Penson
Principal Investigator
Massachusetts General Hospital