Randomized Trial of Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy to Patients With Early Low and Mid Rectal Cancer: The Watchful Waiting 3 Trial (WW3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 162
- 试验地点
- 5
- 主要终点
- Rectal preservation at two years
研究概览
简要总结
In recent years, an increasing number of retrospective and prospective observational studies have indicated that a subset of rectal cancer patients may avoid surgery if they can achieve a complete response to chemoradiotherapy. Prospective trials, including the previous Danish Watchful Waiting trials (NCT00952926, NCT02438839) in early rectal cancer have demonstrated high levels of organ preservation with dose-escalation, but it is unclear whether this was primarily due to tumor stage or dose level.
The aim of the present study is to investigate if a higher dose of radiotherapy is superior compared to a standard dose in patients with early rectal cancer undergoing chemoradiotherapy with curative intent.
详细描述
The main curative treatment modality for rectal cancer is surgery, potentially combined with chemotherapy and radiotherapy to lower the risk of local recurrence. In recent years, an increasing number of retrospective and prospective observational studies have indicated that a subset of patients may avoid surgery altogether if they can achieve a complete response to chemoradiotherapy. These studies have mainly focused on locally advanced tumors with a high risk of local recurrence. Smaller, less advanced tumors appear to respond better to chemoradiotherapy, but the optimal treatment for non-surgical management has not been established. Prospective trials, including the previous Danish Watchful Waiting trials (NCT00952926, NCT02438839) in early rectal cancer have demonstrated high levels of organ preservation with dose-escalation, but it is unclear whether this was primarily due to tumor stage or dose level. High-level evidence is currently absent for the question of radiotherapy dose, especially in early stage cancers.
The aim of the present study is to investigate if a higher dose of radiotherapy is superior compared to a standard dose in patients with early rectal cancer undergoing chemoradiotherapy with curative intent.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically verified adenocarcinoma of the rectum
- •MDT conference finds patient a candidate for rectal resection
- •Clinical tumor category cT1-3
- •MRI findings
- •Maximal cross-sectional size of 4.5 cm (axial plane relative to the rectum)
- •Lowest edge of tumor located at or below the peritoneal reflection on MRI
- •Performance status 0-2
- •Age ≥ 18 years
- •Eligible for radiotherapy and capecitabine according to investigator, including
- •Adequate function of bone marrow (neutrophils ≥ 1.5 x 10^9/l and thrombocytes ≥ 100 x 10^9/l)
- •Adequate function of liver (ALAT < 2.5 x upper limit of normal, bilirubin < 2.5 x upper limit of normal)
- •Adequate kidney function (Serum creatinine < 1.5 x upper limit of normal or measured GFR > 30 ml/min)
- •Fertile women must present a negative pregnancy test and use secure contraceptives during and three months after treatment
- •Written and orally informed consent
排除标准
- •Previous surgical treatment of the present cancer, including transanal excision of tumor
- •Other malignant disease within the past five years except non-melanoma skin cancer and premalignant lesions such as carcinoma in situ
- •Distant metastases verified by imaging or biopsy, i.e. cM1
- •Previous radiation treatment of the pelvis
- •Pregnant or breastfeeding women.
- •Existing colostomy or ileostomy
研究组 & 干预措施
A: Standard chemoradiotherapy
50.4 Gy to the tumor and elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays.
干预措施: 50.4 Gy to the tumor and elective volume (Radiation)
A: Standard chemoradiotherapy
50.4 Gy to the tumor and elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays.
干预措施: Capecitabine 825 mg/m2 twice daily on weekdays (Drug)
B: High-dose radiotherapy
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays
干预措施: 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume (Radiation)
B: High-dose radiotherapy
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays
干预措施: Capecitabine 825 mg/m2 twice daily on weekdays (Drug)
结局指标
主要结局
Rectal preservation at two years
时间窗: 2 years after start of treatment
* Presence of a full-length rectum, i.e. no rectal resection. * Absence of rectal tumor, malignant lymph nodes or any other tumor deposit or recurrence within the pelvis based on clinical examination, CT and MR * No stoma because of side effects to treatment or rectal dysfunction
次要结局
- Colostomy-free survival(At least yearly up to 5 years)
- Frequency of grade 3-4 toxicity according to CTCAE v4(Up to 5 years)
- Rate of complete response within four months from start of radiotherapy(4 months)
- Overall survival(At least yearly up to 5 years)
- Locoregional recurrence (within the pelvis)(At least yearly up to 5 years)
- Quality of life as assessed ny the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29+C30(Up to 5 years)
- Relapse free survival(At least yearly up to 5 years)