Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 314
- 主要终点
- 3-year disease-free survival
研究概览
简要总结
The purpose of this study is to determine whether the combination of paclitaxel, capecitabine, mitomycin and intensity-modulated radiotherapy is more effective than the standard combination of capecitabine, mitomycin and intensity-modulated radiotherapy (IMRT) in patients with squamous-cell anal cancer.
详细描述
This trial aims to investigate the efficacy of chemoradiotherapy with or without paclitaxel in squamous-cell anal cancer. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either standard IMRT with capecitabine and mitomycin or IMRT with capecitabine, mitomycin and paclitaxel. A stratification will be performed based on T stage, N stage and clinical center. Doses of capecitabine and mitomycin in experimental group were reduced for better treatment tolerance. The target accrual is 157 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 15% 3-yr disease-free survival (70% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging and followup. Pelvic MRI and histological diagnosis are subject to central review. Conduction of this study and data collection are controlled by a local institutional board.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Histologically verified squamous-cell anal cancer
- •Stage I-IIIB (Union for International Cancer Control (UICC) TNM classification v7)
- •Eastern Cooperative Oncology Group (ECOG) status 0-2
- •HIV (Human Immunodeficiency Virus) negative
- •Haemoglobin (HGB) > 90 g/L
- •Platelet Count (PLT) > 120x10*9/L
- •Serum creatinine < 150 µmol/L
- •Total bilirubin < 25 µmol/L
排除标准
- •inability to obtain informed consent
- •distant metastases
- •synchronous or metachronous tumors
- •previous chemotherapy or radiotherapy
- •clinically significant cardiovascular disorders (myocardial infarction < 6 months before visit, stroke < < 6 months before visit, instable angina < 3 months before visit, arrhythmia, uncontrolled hypertension > 160/100 mm hg
- •clinically significant neurological disorders
- •previous neuropathy 2 or higher
- •current infection or heavy systemic disease
- •pregnancy, breastfeeding
- •ulcerative colitis
- •individual intolerance to treatment components
- •proven dihydropyrimidine dehydrogenase (DPD) deficiency
- •participation in other clinical trials
- •psychiatric disorders, which render patient unable to follow instructions or understand his/her condition
- •technical inability to perform pelvic MRI
- •inability of long-term followup of the patient
研究组 & 干预措施
Paclitaxel
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.
干预措施: Paclitaxel (Drug)
Paclitaxel
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.
干预措施: Capecitabine (Drug)
Paclitaxel
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.
干预措施: Mitomycins (Drug)
Paclitaxel
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.
干预措施: Radiotherapy (Radiation)
Standard
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1.
干预措施: Capecitabine (Drug)
Standard
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1.
干预措施: Mitomycins (Drug)
Standard
Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
3-year disease-free survival
时间窗: 3 years
次要结局
- 3-year cancer-specific survival(3 years)
- 3-year colostomy-free survival(3 years)
- Complete response at 26 weeks(26 weeks)
- 3-year overall survival(3 years)
- Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0(30 days)
- Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria(3 years)
研究者
Sergey Gordeyev
Principal Investigator
Blokhin's Russian Cancer Research Center