A Phase I Trial of Intravenous Paclitaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Docetaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Paclitaxel, Intraperitoneal Carboplatin, Intraperitoneal Paclitaxel and CTEP-Supplied Agent Bevacizumab (NSC 704865, IND 7921) in Patients With Previously Untreated Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 16
- 主要终点
- MTD of IV paclitaxel with IP carboplatin and IV bevacizumab followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of intraperitoneal infusions of carboplatin when given together with intravenous infusions of either docetaxel or paclitaxel followed by intraperitoneal paclitaxel in treating patients with stage II, stage III, or stage IV ovarian epithelial, fallopian tube, or primary peritoneal cavity carcinoma (cancer). Drugs used in chemotherapy, such as carboplatin, docetaxel, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of intraperitoneal (IP) carboplatin when given in combination with IV paclitaxel followed by IP paclitaxel in patients with stage III or IV ovarian epithelial, fallopian tube, or primary peritoneal cavity carcinoma.
II. Determine the MTD of IP carboplatin and IV docetaxel when given in combination with IP paclitaxel in these patients.
III. To determine the feasibility of the combination of IV paclitaxel, IP carboplatin and IV bevacizumab on day one followed by IP paclitaxel on day eight (Part C Only).
IV. Determine the dose-limiting toxic effects and complications in patients treated with these regimens.
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 fallopian tube, ovarian epithelial, or primary peritoneal carcinoma
- •Stage II-IV disease
- •The following epithelial cell types are allowed:
- •Carcinosarcoma
- •Serous adenocarcinoma
- •Endometrioid adenocarcinoma
- •Mucinous adenocarcinoma
- •Undifferentiated carcinoma
- •Clear cell adenocarcinoma
- •Mixed epithelial carcinoma
- •Transitional cell carcinoma
- •Malignant Brenner's tumor
- •Adenocarcinoma not otherwise specified
- •Must have undergone prior surgery for ovarian or peritoneal carcinoma within the past 12 weeks
- •Optimal (≤ 1 cm residual disease) or suboptimal residual disease following initial surgery
- •Must have a procedure for determining diagnosis of ovarian/peritoneal carcinoma with appropriate tissue for histologic evaluation
- •Synchronous primary endometrial cancer or prior endometrial cancer allowed provided the following criteria are met:
- •Stage ≤ IB
- •Less than 3 mm invasion without vascular or lymphatic invasion
- •No poorly differentiated subtypes (e.g., grade 3, clear cell, or papillary serous)
- •No epithelial ovarian carcinoma of low malignant potential (borderline carcinomas)
- •No CNS disease (e.g., seizures not controlled with standard medical therapy) or metastasis
- •GOG performance status 0-2
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus) (applies to part C only)
- •PTT < 1.2 times the upper limit of normal (applies to part C only)
- •SGOT ≤ 2.5 times normal
- •Alkaline phosphatase ≤ 2.5 times normal
- •Bilirubin ≤ 1.5 times normal
- •Creatinine ≤ 1.5 times normal
- •No active bleeding
- •Abnormal cardiac conduction (e.g., bundle branch block or heart block) allowed provided disease has remained stable for the past 6 months
- •No unstable angina or myocardial infarction within the past 6 months
- •No neuropathy (sensory and motor) > CTCAE grade 1
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
- •No septicemia, severe infection, or acute hepatitis
- •No other invasive malignancy within the past 5 years except non-melanoma skin cancer or localized breast cancer
- •No circumstance that would preclude study participation
- •No history of allergic reaction to polysorbate 80 (e.g., etoposide or vitamin E)
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies (applies to part C only)
- •No clinically significant proteinuria
- •Must have urine protein-creatinine ratio (UPCR) < 1
- •No serious, non-healing wound, ulcer, or bone fracture (applies to part C only)
- •At least 3-6 months since prior abdominal fistula or gastrointestinal perforation and fully recovered (part C only)
- •No history of intra-abdominal abscess within the past 28 days (applies to part C only)
- •No active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels (applies to part C only)
- •No history or evidence (upon physical examination) of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases (applies to part C only)
- •No history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study (applies to part C only)
- 另有 18 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab)
Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab)
Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel (Drug)
Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab)
Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab)
Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 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
MTD of IV paclitaxel with IP carboplatin and IV bevacizumab followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0
时间窗: 3 weeks
Maximum tolerated dose (MTD) of IV paclitaxel with IP carboplatin followed by IP 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
MTD of IV docetaxel with IP carboplatin followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0
时间窗: 3 weeks
次要结局
- Incidence of adverse events in patients given of IV docetaxel with IP carboplatin followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0(12 weeks)
- Incidence of adverse events in patients given IV paclitaxel with IP carboplatin and IV bevacizumab followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0(12 weeks)
- Incidence of adverse events in patients given IV paclitaxel with IP carboplatin followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0(12 weeks)