A Phase III Study Evaluating Two Neoadjuvant Treatments Radiochemotherapy (5 Weeks - 50Gy+Capecitabine) and Radiotherapy (1week - 25Gy) in Patient Over 75 With Locally Advanced Rectal Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- UNICANCER
- 入组人数
- 103
- 试验地点
- 37
- 主要终点
- R0 resection rate
研究概览
简要总结
The purpose of the study is to compare pre-operative radio-chemotherapy (RT + capecitabine) to a short course RT associated with a delayed surgery, with two primary objectives: the efficacy evaluation (rate of R0 resection) and the preservation of autonomy (score IADL).
详细描述
Colorectal cancer is one of the most frequent cancers diagnosed in France. The average age of diagnosis in 2012 was 70 years old for men and 73 years for women, confirming that colorectal cancer is a disease of the elderly population.
The literature concerning combined treatments of colorectal cancer in the elderly is extremely limited. The application of combined treatments in the geriatric population is associated with an increase in the therapeutic complications. These post-operative complications together with the comorbidities and age are unfavorable prognostic factors for survival in patients with cancer of the rectum; this explains why the improved results obtained during the last decades are perceptible in younger patients and not in the elderly.
In the general population, pre-operative radio-chemotherapy has imposed itself as a standard treatment for the cancer of the rectum locally advanced. The utilization of fluoropyrimidines associated with radiotherapy (RT) delivered in fractions [long course RT (50 Gy in 5 weeks), surgery planned 6 to 8 weeks later] increases the complete histological response rate and decreases significantly the rate of local relapse.
The short-course RT [short course RT using the Swedish model (5x5 Gy in 5 days), with the surgery programmed the following week] is the standard neoadjuvant protocol in an important number of countries and/or academic groups. The studies that have compared the fractioned RT scheme to the short-course RT protocols have not shown any evidence of a change in efficacy of the short course RT concerning the following criteria: rate of R0 resection, rate of sphincter conservation, rate of relapse at 3 years, the disease free survival or the overall survival. Similarly, there appears to be no difference in severe toxicities in the long term. It should however be noted that short-course RT followed by immediate surgery may be less efficient than combined treatment in patients with a distal T3 cancer, even though these conclusions published by Ngan have been criticized by certain. On the other hand, the fractioned combined treatments results in more tumor and stage reduction and thus more sterilization.
Nevertheless a retrospective analysis, performed in the Stockholm region, in patients irradiated with short-course protocol but operated with a delay of at least 4 weeks resulted in a sterilization rate of 8%. This result is even more interesting since in this cohort, 46% of the patients had a tumor classified T4 and that 38% of the patients had a primitive tumor considered inoperable.
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
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥75 years
- •Eastern Cooperative Oncology Group (ECOG) ≤2
- •Adenocarcinoma of the rectum histologically proven
- •Tumor ≤12 cm from the anal margin, the measurement done by rigid rectoscopy or by sub peritoneal MRI
- •Require a pre-operative treatment (tumor classified T3 or T4 resectable by MRI and tomodensitometry or T2 of the very low rectum)
- •Patient operable
- •No radiologically detectable metastases
- •Absolute Neutrophile count (ANC) ≥1500/mm³; Platelets ≥100 000/mm³ and Hemoglobin ≥10 g/dL
- •Bilirubin ≤1.5 x upper limit of normal (ULN), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤1.5 x upper limit of normal (ULN), Alkaline Phosphatase ≤1.5 x upper limit of normal (ULN)
- •Creatinine clearance ≥30 ml/min (Cockcroft and Gault)
- •Uracilemia < 16ng/mL
- •Public or private Health Insurance coverage
- •Patient has been informed and signed the informed consent document
排除标准
- •Non-resectable tumor
- •History of chronic diarrhea or an inflammatory disease of the colon or rectum, or intestinal obstruction or sub-obstruction
- •History of pelvic radiotherapy
- •Any active febrile infection or any other serious underlying pathology that may prevent the patient from receiving the treatment
- •Significant Cardiovascular diseases such as, but not limited to: cardiovascular or myocardial infarction ≤6 months before inclusion, congestive heart failure class II or higher (NYHA), unstable angina, arrhythmia requiring medication or uncontrolled hypertension;
- •Significative cardiovascular conditions such as, but not limited to : Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery Symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA), clinically significant irregular heartbeat requiring medication
- •Severe and unexpected reactions to fluoropyrimidine therapy
- •Any contra-indication to capecitabine and its excipients; patients with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not included.
- •Uracilemia ≥ 16ng/mL
- •Any other concomitant cancer or history of cancer in the last 3 years, with the exception of the in situ cancer of the uterus, treated, or squamous-cell or basal-cell carcinoma.
- •Patients already included in another therapeutic trail with an experimental molecule
- •Person deprived of liberty
- •Patient that for geographical, social and/or physical reasons will not be able to follow the procedure as required by the protocol
研究组 & 干预措施
Radiochemotherapy
Patients who will be treated with
- radiotherapy 50 Gy in 25 fractions of 2 Gy, five times per week, over a period of 5 weeks associated with
- oral capecitabine 800 mg/m2 twice daily from the first day of radiotherapy and given 5 days per week during radiotherapy.
The surgery will be planned 7 weeks (±1 week) after the end of preoperative treatment
干预措施: 50 Gy (Radiation)
Radiochemotherapy
Patients who will be treated with
- radiotherapy 50 Gy in 25 fractions of 2 Gy, five times per week, over a period of 5 weeks associated with
- oral capecitabine 800 mg/m2 twice daily from the first day of radiotherapy and given 5 days per week during radiotherapy.
The surgery will be planned 7 weeks (±1 week) after the end of preoperative treatment
干预措施: Capecitabine (Drug)
Radiotherapy
Patients who will be treated with radiotherapy 25 Gy in 5 fractions of 5 Gy delivered in one week (short-course arm) without chemotherapy.
The surgery will be planned 7 weeks (±1 week) after the end of preoperative treatment
干预措施: 25 Gy (Radiation)
结局指标
主要结局
R0 resection rate
时间窗: 3 months
Compare the efficacy between the arm A and the arm B (with an objective of non-inferiority)
IADL (Instrumental Activities of Daily Living) Score
时间窗: 1 year
Compare the maintenance of autonomy between the arm A and arm B (with an objective of superiority)
次要结局
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03(3 months)
- Questionnaire G8(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Post-operative complications(3 months)
- Death rate(at 6 and 12 months)
- Disease free survival(10 years)
- Mini-Mental Score Examination (MMSE)(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Geriatric Depression Scale (GDS15)(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Overall survival (OS)(10 years)
- Specific survival(10 years)
- Loco-regional disease free survival(10 years)
- Rate of stoma(at 6 and 12 months)
- Activities of Daily Living (ADL)(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Walking gate(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Charlson score(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Mini Nutritional Assessment (MNA)(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- Instrumental Activities of Daily Living (IADL)(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)
- EORTC QLQ-C30 + EDL14(Baseline, within 2 weeks before surgery and 3, 6 and 12 months after surgery)