A Phase I Trial of Tailored Radiation Therapy With Concomitant Cetuximab (C225, NSC #714692) and Cisplatin (NSC #119875) in the Treatment of Patients With Cervical Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 15
- 主要终点
- Maximum tolerated dose (MTD) or biologically effective dose (BED) of Cetuximab in combination with cisplatin and extended field radiation or whole pelvis radiation, 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 cetuximab when given together with cisplatin and radiation therapy in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer. Monoclonal antibodies, such as cetuximab, 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. Drugs used in chemotherapy, such as 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 and other types of radiation to kill tumor cells. Internal radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving cetuximab together with cisplatin and radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose or safe biologically effective dose of cetuximab when administered in combination with cisplatin, external beam radiotherapy, and brachytherapy in patients with stage IB-IVA cervical cancer.
II. Determine the feasibility of this regimen, in terms of chronic and acute toxic effects, in these patients.
SECONDARY OBJECTIVES:
I. Determine the distribution of progression-free survival and overall survival of patients treated with this regimen at 1 year after study entry.
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 cancer
- •Clinical stage IB-IVA disease
- •Any cell type allowed
- •Positive or negative pelvic and/or para-aortic lymph nodes by radiography
- •Unstained sections from primary tumor available
- •Performance status - GOG 0-1
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •SGOT ≤ 2.5 times ULN
- •Alkaline phosphatase ≤ 2.5 times ULN
- •Creatinine normal
- •Creatinine clearance > 50 mL/min
- •Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
- •No renal abnormality (e.g., pelvic kidney or horseshoe kidney) that would require modification of radiation fields
- •No significant cardiac disease within the past 6 months, including any of the following:
- •Uncontrolled hypertension
- •Unstable angina
- •Congestive heart failure
- •Uncontrolled arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No sensory or motor neuropathy > grade 1
- •No septicemia
- •No severe infection
- •No circumstance that would preclude study participation or follow-up
- •No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
- •No uncontrolled seizure disorder
- •No active neurologic disease
- •No history of active collagen vascular disease
- •No prior chimerized or murine monoclonal antibody therapy
- •No prior cytotoxic chemotherapy for cervical cancer
- •No prior pelvic or abdominal radiotherapy for cervical cancer
- •No concurrent intensity modulated radiotherapy
- •No prior renal transplantation
- •More than 30 days since prior major surgery (excluding diagnostic biopsy)
- •No other prior therapy for cervical cancer
- •No prior cancer treatment that would preclude study therapy
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (brachytherapy, radiation, cetuximab, cisplatin)
Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Internal Radiation Therapy (Radiation)
Treatment (brachytherapy, radiation, cetuximab, cisplatin)
Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (brachytherapy, radiation, cetuximab, cisplatin)
Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Cetuximab (Biological)
Treatment (brachytherapy, radiation, cetuximab, cisplatin)
Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks 4-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) or biologically effective dose (BED) of Cetuximab in combination with cisplatin and extended field radiation or whole pelvis radiation, graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
时间窗: 6 weeks
Evaluation of the regimens will be conducted separately by the type of radiation received (extended field radiation or whole pelvis radiation).
Incidence of toxicities at the MTD, assessed by CTCAE v3.0
时间窗: Up to 1 year
次要结局
- Progression-free survival(From study entry until disease progression, death or date of last contact, up to 1 year)
- Site of recurrence, loco-regional vs distant, assessed by clinical and radiological evaluation(From study entry until disease progression, death or date of last contact, up to 1 year)
- Frequency of chronic toxicities, assessed by CTCAE v3.0(From study entry until disease progression, death or date of last contact, up to 1 year)