A Phase I Study of Adjuvant Topotecan and Cisplatin With Concurrent Radiation Therapy for Advanced Cervical Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of topotecan
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as topotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Topotecan and cisplatin may make tumor cells more sensitive to radiation therapy. Giving topotecan and cisplatin together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of topotecan when given together with cisplatin and radiation therapy in treating patients with advanced cervical cancer.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of topotecan when administered with cisplatin in patients with advanced cervical cancer.
- Identify any unique toxicities associated with administering radiotherapy along with adjuvant cisplatin and topotecan in patients with cervical cancer.
- Determine the feasibility of administering continuous infusion topotecan chemotherapy together with radiation therapy.
- Assess the quality of life of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of topotecan.
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
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 cervical carcinoma
- •Deemed not curable by surgery or radiotherapy alone
- •The following stages are eligible:
- •Stage IIB
- •Stage IIIA or IIIB
- •Stage IVA
- •Stage IB or IIA with ≥ 1 of the following risk factors:
- •Primary tumor ≥ 6 cm
- •Positive pelvic and/or para-aortic lymph nodes (resected or unresected)
- •Positive surgical margins
- •Depth of invasion > 50% and positive capillary-lymphatic space involvement
- •The following histologic subtypes are eligible:
- •Adenosquamous
- •Adenocarcinoma
- •No recurrent cervical cancer
- •Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
- •White blood cells (WBC) ≥ 3,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Granulocyte count ≥ 1,500/mm^3
- •Creatinine ≤ 2.0 mg/dL
- •Bilirubin ≤ 1.5 times institutional normal
- •Serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase ≤ 3 times institutional normal
- •No other prior or concurrent malignancies other than skin (excluding melanoma)
- •No septicemia, severe infection, gastrointestinal bleeding, or intestinal obstruction
- •No anatomic abnormalities (e.g., pelvic kidney or renal transplant) requiring modification of radiation fields
- •Fertile patients must use effective contraception
- •Negative pregnancy test
- •Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) are eligible if disease is stable for the past 6 months
- •Recovered from recent surgery
排除标准
- •Prior pelvic radiation
- •Pregnant or nursing
- •History of thrombus
- •History of unstable angina or myocardial infarction within the past 6 months
研究组 & 干预措施
Combo Chemotherapy and Radiation
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: cisplatin (Drug)
Combo Chemotherapy and Radiation
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: topotecan hydrochloride (Drug)
Combo Chemotherapy and Radiation
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: brachytherapy (Radiation)
Combo Chemotherapy and Radiation
Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Maximum tolerated dose of topotecan
时间窗: Week 3 After First Course of Therapy
Adequate Response Trial Minimum length of trial to evaluate response is defined as receiving the first course of chemotherapy and living at least three weeks for repeat measurement to be performed.
次要结局
未报告次要终点