Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- UNICANCER
- 入组人数
- 19
- 试验地点
- 10
- 主要终点
- Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving radiation therapy together with combination chemotherapy and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and cetuximab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II clinical trial is studying how well giving radiation therapy together with chemotherapy and cetuximab followed by surgery, chemotherapy, and cetuximab works in treating patients with locally advanced or metastatic rectal cancer that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- Determine the complete remission rate at 6 months after neoadjuvant radiotherapy, capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).
Secondary
- Determine progression-free survival.
- Determine overall survival.
- Assess toxicities.
- Evaluate objective response in patients with measurable metastases.
- Determine the rate of local recurrence.
- Evaluate the downstaging and downsizing of patients with operable disease.
- Evaluate surgical complications in patients with operable disease.
- Evaluate biological markers predictive of response to cetuximab.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed adenocarcinoma of the rectum
- •Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease
- •Metastases must be resectable
- •Primary tumor examined by endorectal echography and MRI
- •Measurable disease by thoraco-abdomino-pelvic scanner
- •Disease considered susceptible to treatment with radiotherapy and chemotherapy
- •No diffuse metastases considered nonresectable
- •No acute occlusion not caused by colostomy
- •PATIENT CHARACTERISTICS:
- •Inclusion criteria:
- •ECOG performance status 0-2
- •WBC ≥ 4,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Creatinine ≤ 130 µmol/L
- •Transaminases ≤ 5 times upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 times ULN
- •Alkaline phosphatase ≤ 2.5 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients of must use effective contraception
排除标准
- •Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or radiotherapy
- •Impossible to perform translational analyses
- •Uncontrolled severe illness
- •Severe renal or hepatic insufficiency
- •Cardiac insufficiency or symptomatic coronary disease
- •Sensitive peripheral neuropathy
- •Uncontrolled diabetes
- •Other malignancy within the past 10 years except previously treated basal cell skin cancer or carcinoma in situ of the cervix
- •Impossible to participate in study due to geographic, social, or psychiatric reasons
- •Patients who are under supervision or incarcerated
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No prior anticancer chemotherapy or radiotherapy for this cancer
- •No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids, or allopurinol
- •No concurrent participation in another therapeutic study or receiving another experimental drug
结局指标
主要结局
Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
次要结局
- Sexual function
- Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
- Sphincter function
- Preoperative clinical response
- Progression-free survival
- Late toxicity
- Late radiotherapy toxicity by CTC AE v. 3.0
- Overall survival
- Early toxicity before surgery
- Surgical complications
- Objective response of measurable metastases by RECIST
- Downstaging and downsizing of patients with operable disease
- Predictive biomarkers of response to cetuximab