Phase II Trial of Fenretinide (NSC 374551) in Recurrent Ovarian Cancer and Primary Peritoneal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Response rate (CR or PR)
研究概览
简要总结
Phase II trial to study the effectiveness of fenretinide in treating patients who have recurrent or metastatic ovarian epithelial or primary peritoneal cancer. Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of fenretinide (4-HPR) in patients with recurrent ovarian cancer or primary peritoneal carcinoma.
II. To assess the toxicity of this agent in this patient population. III. To evaluate molecular changes in normal and tumor cells induced by 4-HPR by studying: (a) the analysis of ceramide and glucosyleceramide levels before and after therapy, (b) intracellular levels of 4-HPR and 4-MPR, and (c) determinants of apoptosis (p53, p21, bcl-2, bax and terminal deoxynucleotidyl transferase [TdT] assay) in baseline tumor specimens, serial serum and tumor biopsy specimens where available, and surrogate in-vitro studies.
IV. To evaluate the pharmacokinetics of fenretinide. V. To further investigate the antiangiogenesis effects of fenretinide in in-vitro assays using ovarian cancer cell lines and in vascular growth factor (VEGF, TGFb) plasma levels in patients.
OUTLINE:
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed recurrent or metastatic epithelial ovarian cancer or primary peritoneal carcinoma
- •Unidimensionally measurable disease; indicator lesions must not have been irradiated unless they have grown following radiation therapy
- •SWOG performance status 0-2
- •Patients must have received a platinum and paclitaxel containing regimen
- •Patients are allowed to receive =< 2 prior chemotherapy regimens for recurrent disease; patients who are rechallenged with the same chemotherapy regimen are considered to have had that regimen only once
- •Projected life expectancy must be at least 3 months
- •Signed informed consent
- •Absolute neutrophil count >= 1500/ul
- •Platelet count >= 100,000 ul
- •Bilirubin =< 2 times the institutional limit of normal
- •ALT or AST =< 3 times the upper limit of normal
- •Measured or calculated creatinine clearance >= 60 ml/min
- •Fasting triglycerides =< 1 time the upper limit of normal; triglycerides may be "normalized" prior to study entry with use of an antilipemic agent (atorvastatin, fenofibrate)
- •Patients must have recovered from acute toxicities from surgery, radiation or chemotherapy; at least 3 weeks will have elapsed since any prior therapy directed at the malignant tumor
- •Patients of childbearing potential must agree to use an approved method of birth control
排除标准
- •Prior fenretinide is not allowed; prior 13-cis, 9-cis or all-transretinoic acid are allowed
- •Patients with a second malignancy within the last 5 years are not allowed, except for those with non-melanomatous skin cancer and carcinoma-in-situ of the cervix; all prior invasive malignancies must be in complete remission
- •The use of concomitant antioxidants, such as vitamin C or E, is not allowed
- •Patients with concurrent medical, psychological or social conditions of such severity that the investigator deems it unwise to enter the patient on protocol
- •Untreated or symptomatic brain metastases
- •Pregnant or nursing women
研究组 & 干预措施
Treatment (fenretinide)
Patients receive oral fenretinide twice daily on days 1-7. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: fenretinide (Drug)
Treatment (fenretinide)
Patients receive oral fenretinide twice daily on days 1-7. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (fenretinide)
Patients receive oral fenretinide twice daily on days 1-7. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Response rate (CR or PR)
时间窗: Up to 9 years
Associated exact 95% confidence intervals will be calculated.
次要结局
- Time to treatment failure(up to 9 years)
- Duration of response(From the time measurement criteria met for CR/PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years)
- Overall survival(From first day of treatment to time of death due to any cause, assessed up to 9 years)
- Toxicity(Up to 9 years after completion of treatment)
- Pharmacokinetics of fenretinide(Baseline. day 1, 4 and 7 of courses 1, day 1 of courses 2, 5, and 9, day 7 of courses 4 and 8)
- Molecular change(Baseline to end of treatment)