A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of Intraperitoneal Carboplatin (NSC #214240) and Intravenous Paclitaxel (NSC # 673089) and Intravenous Paclitaxel, Intraperitoneal Carboplatin and NCI Supplied Intravenous Bevacizumab (NSC #704865) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 19
- 主要终点
- Maximum tolerated dose (MTD) of intraperitoneal carboplatin with intravenous paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
研究概览
简要总结
This phase I trial is studying the side effects and best dose of adjuvant intraperitoneal carboplatin when given together with paclitaxel and bevacizumab in treating patients who have undergone debulking surgery for stage II , stage III, or stage IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are more effective than carboplatin and paclitaxel in treating ovarian epithelial or primary peritoneal cancer, or fallopian tube cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of intraperitoneal carboplatin when administered with paclitaxel during course 1, in patients with stage II-IV ovarian epithelial, primary peritoneal, or fallopian tube cancer who had initial debulking surgery.
II. Determine the feasibility of this regimen in these patients. III. Determine the feasibility of adding IV bevacizumab to this regimen in courses 2-6.
SECONDARY OBJECTIVES:
I. Determine the toxicity profile of this regimen in these patients. II. Determine the toxicity profile of paclitaxel and bevacizumab IV in combination with intraperitoneal carboplatin in these patients.
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 ovarian epithelial, primary peritoneal, or fallopian tube cancer
- •Stage II-IV disease
- •The following histologic epithelial cell types are eligible:
- •Serous adenocarcinoma
- •Mucinous adenocarcinoma
- •Clear cell adenocarcinoma
- •Transitional cell carcinoma
- •Adenocarcinoma not otherwise specified
- •Endometrioid adenocarcinoma
- •Undifferentiated carcinoma
- •Mixed epithelial carcinoma
- •Malignant Brenner's tumor
- •Optimal (≤ 1 cm residual disease) OR suboptimal residual disease after initial debulking surgery (performed within the past 12 weeks)
- •Synchronous primary endometrial cancer OR prior history of endometrial cancer allowed provided all of the following are true:
- •Stage IB disease or less
- •Less than 3 mm invasion without vascular or lymphatic invasion
- •No poorly differentiated subtypes, including the following:
- •Papillary serous
- •Clear cell
- •Other FIGO grade 3 lesions
- •No epithelial tumors of low malignant potential (borderline tumors)
- •No CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases by history or evidence upon physical examination within the past 6 months
- •Performance status - GOG 0-2
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •INR ≤ 1.5
- •PTT < 1.2 times upper limit of normal (ULN)
- •No active bleeding or pathologic conditions carrying high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
- •AST ≤ 3 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 3 times ULN
- •Bilirubin ≤ 1.5 times ULN
- •No acute hepatitis
- •Creatinine ≤ 2.0 mg/dL
- •Urine protein-creatinine ratio < 1.0 OR protein 1.0 g by 24 hour urine collection
- •Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided the patient's cardiac status has been stable for ≥ 6 months before study entry
- •No clinically significant cardiovascular disease, including any of the following:
- •Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
- •Myocardial infarction or unstable angina within the past 6 months
- •New York Heart Association class II-IV congestive heart failure
- •Serious cardiac arrhythmia requiring medication
- •Peripheral vascular disease ≥ CTCAE grade 2 (at least brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit)
- •No history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within the past 6 months
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for ≥ 6 months after completion of bevacizumab therapy
- •No neuropathy (sensory and motor) > grade 1
- •No active infection requiring antibiotics
- •No circumstances that would preclude study participation
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
- •No history of allergic reaction to polysorbate 80 (e.g., etoposide, vitamin E)
- •No other invasive malignancies within the past 5 years except non-melanoma skin cancer or localized breast cancer
- 另有 17 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: adjuvant therapy (Procedure)
Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel (Drug)
Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Treatment (adjuvant, paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15 minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bevacizumab (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) of intraperitoneal carboplatin with intravenous paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
时间窗: 3 weeks
Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel at the MTD, assessed by CTCAE v3.0
时间窗: 12 weeks
Number of observed DLTs in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0
时间窗: 6 weeks
次要结局
- Incidence of adverse events in patients given intraperitoneal carboplatin with intravenous paclitaxel and intravenous bevacizumab, graded using CTCAE v3.0(12 weeks)
- Response rate (in patients with measurable disease who are in the expanded cohort) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)(Up to 1 year)
- Progression-free survival assessed by RECIST(From study entry until disease progression, death or date of last contact, up to 1 year)