Phase II Trial- Weekly Taxotere and Topotecan for Recurrent Ovarian, Primary Peritoneal, Endometrial and Uterine Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- To determine the overall clinical response rate of weekly Topotecan and Taxotere in women with recurrent ovarian, primary peritoneal, endometrial and uterine cancers
研究概览
简要总结
The primary aim of this study is:
- To determine the overall clinical response rate of weekly Topotecan and Taxotere in women with recurrent ovarian, primary peritoneal, endometrial and uterine cancers.
The secondary aims of this study are:
- To evaluate the safety and tolerability of the combination therapy with weekly Topotecan and Taxotere in patients with recurrent ovarian, primary peritoneal, endometrial or uterine cancers.
- To determine the progression free survival and overall survival in women treated with weekly Topotecan and Taxotere in patients with recurrent ovarian, primary peritoneal, endometrial and uterine cancers who have been previously treated with chemotherapy and/or radiation therapy.
详细描述
Endometrial carcinoma is the most common gynecologic cancer, accounting for 6,500 deaths in 2002 in the United States. There has been a 128% increase in endometrial cancer deaths over the past decade mainly due to recurrences. Although primary surgery with or without adjuvant therapy can cure most patients, effective therapy for those patients with advanced or recurrent disease is needed. Due to the advanced age of this patient population and associated medical comorbidities, these patients are not always ideal candidates for experimental therapies exploring dose intensity or toxic agents. Treatment options for advanced or recurrent disease are limited. Cytotoxic therapy has made little impact on survival.
Recent data has demonstrated efficacy of Topotecan in advanced or recurrent endometrial cancer. A Phase II trial performed primarily by the New York Gynecologic Oncology Group through ECOG found Topotecan to be an active first line treatment for metastatic or recurrent endometrial cancer. The overall response rate was 20% with 3/40 patients complete responders. A Phase II trial by the Gynecologic Oncology Group (GOG) of 29 patients with advanced or recurrent endometrial cancer reported a 10% overall response rate to 5-day intravenous Topotecan. However, 55% of patients had stable disease. Reported side effects were mainly hematologic, specifically, neutropenia and thrombocytopenia. Finkler and Holloway reported a phase I/II trial using weekly Topotecan in recurrent endometrial cancer. 23% of patients had partial response to therapy, with a decrease in grade 4 neutropenia and thrombocytopenia compared to the 5-day infusion. In a pilot study examining the role of 5-day Topotecan in uterine papillary serous carcinoma (UPSC), Chambers et al. report 11 of 12 patients who received Topotecan as front-line therapy to be disease-free at 13 months median follow-up. Anemia and neutropenia were managed effectively with hematopoietic stimulating factors.
Taxanes have also been reported to be effective in the treatment of advanced and recurrent endometrial cancer. Endometrial cancer cell lines have demonstrated sensitivity to paclitaxel. Response rates of 35%-37% have been reported in two separate phase II trials. Günthert et al., reported a complete response to Taxotere in a patient with recurrent endometrial cancer.
Taxotere is an agent well documented in the management of advanced ovarian cancer, with a response rate of approximately 30% in platinum-refractory patients. Taxotere has also demonstrated clinical response in patients classified as paclitaxel-refractory, confirming an incomplete cross-resistance between these two agents. Based on these data, there is reason to believe that the combination of Topotecan and Taxotere in the second-line setting may prove promising in patients initially treated with paclitaxel and platinum-based therapy.
Topotecan and Taxotere have known activity in ovarian cancer patients. Recent weekly dosing schedules suggest similar activity in ovarian cancer patients with less toxicity. Ovarian cancer patients who have significant Taxane-related side effects, including neuropathy, do well with weekly Taxotere. Both Topotecan and Taxotere have documented efficacy in recurrent endometrial cancer, but no study, to date, has utilized them in combination for the treatment of endometrial cancer. In addition to utilizing this regimen in a phase II setting for recurrent ovarian cancer, we propose a phase II trial utilizing this combination for the treatment of recurrent endometrial cancer. The justification for including all of these tumor types in the same protocol is the known similar response rates of these Gynecologic tumors to all chemotherapies. The endpoints and power are designed for all of the histologic types, but subset analysis will be used for each tumor type after completion of the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 documented recurrent endometrial adenocarcinoma, papillary serous (UPSC), or mixed mullerian tumor (MMT) for which a cure or substantial palliation is unlikely using surgery and/or radiotherapy. Patients must have measurable disease or disease felt to be reproducibly measurable on CT scan, chest x-ray and/or tumor marker elevations .
- •Recurrent ovarian or primary peritoneal cancers as defined as either:
- •Measurable disease either by physical examination or by imaging or
- •Non-measurable evidence of disease such as any or all of the following standard Rustin criteria:
- •Peritoneal implants <2 cm
- •Abnormal densities on computerized tomography (CT) scan and/or loculated fluid collections
- •Elevated CA-125 (>100 U/mL on 2 measurements at least 1 week apart) and disease- related symptoms.
- •Patients with the following histologic ovarian or uterine epithelial cell types are eligible:
- •Serous adenocarcinoma
- •Endometrioid adenocarcinoma
- •Mucinous adenocarcinoma
- •Undifferentiated carcinoma
- •Clear cell adenocarcinoma
- •Mixed epithelial carcinoma
- •Transitional cell
- •Malignant Brenner's tumor
- •Adenocarcinoma NOS
- •Age ≥ 18 years.
- •ECOG performance status of ≤
- •Peripheral neuropathy must be ≤ grade 1
- •Previously treated patients must have received no antineoplastic treatment for at least 4 weeks. Patients will not have received more than two previous chemotherapy regimens.
- •In patients previously irradiated, the recurrent disease should be outside of the radiotherapy portal or have developed disease progression within the radiated field.
- •No concurrent chemotherapy, radiotherapy, immunotherapy, or hormone therapy.
- •Total bilirubin ≤ ULN
- •AST and ALT and alkaline phosphatase must be within the range allowing for eligibility.
- •Patients must be alert, oriented, and have signed an informed consent in accordance with institutional policies and be aware of the investigational nature of the study.
- •Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
排除标准
- •Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
- •Serum creatinine clearance ≤ 50 ml/min
- •Platelets <100,000/mm3
- •Absolute neutrophil count (ANC) <1500/mm3
- •Hemoglobin <8.0 g/dl (the patient may be transfused prior to study entry)
- •History of chronic or active hepatitis
- •Patient has severe or uncontrolled medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
- •Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at time of study entry.
- •Patients with a history of severe hypersensitivity to Taxotere®, Topotecan®, or other drugs formulated with polysorbate
- •Women who are pregnant or breast-feeding
结局指标
主要结局
To determine the overall clinical response rate of weekly Topotecan and Taxotere in women with recurrent ovarian, primary peritoneal, endometrial and uterine cancers
次要结局
- To evaluate the safety and tolerability of weekly Topotecan and Taxotere in patients with recurrent ovarian, primary peritoneal, endometrial or uterine cancers
- To determine the progression free survival and overall survival with weekly Topotecan and Taxotere in patients with recurrent ovarian, primary peritoneal, endometrial and uterine cancers who have been previously treated with chemotherapy
研究者
Mark H. Einstein
Director, Clinical Research for Women's Health
Montefiore Medical Center