Dose Escalated Adaptive RadioTherapy - a Randomised Phase II Study of Definitive Chemo-radiotherapy in Locally Advanced Esophageal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 6
- 主要终点
- Loco-regional control
研究概览
简要总结
In Denmark, 1000 new cases of esophageal and gastro-esophageal junction cancer occur every year. Surgery is the primary treatment for patients with localized disease who are considered medically and technically operable. For patients deemed non-resectable, definitive chemoradiotherapy is the treatment of choice, but despite treatment with curative intent, these patients have a poor prognosis, with a median survival of less than 20 months and a 5-year survival at 15-25% in clinical studies
This study will examine the effect of escalation of increasing the radiation dose to the most Positron Emissions Tomografi (PET) avid part of the tumour and lymph nodes compared to a standard uniform dose distribution.
详细描述
In Denmark, there are almost 900 new cases of oesphageal and gastro-esophageal junction (GEJ) cancer per year, with a 5-year survival rate below 20% for the entire group and a 5-year survival rate of approximately 40% for the curatively treated patients.
Surgery is the primary treatment for patients with localized disease who are considered medically and technically operable. For patients deemed non-resectable, definitive chemoradiotherapy is the treatment of choice, but despite treatment with curative intent, these patients have a poor prognosis, with a median survival of less than 20 months and a 5-year survival at 15-25% in clinical studies.
Survival is affected by several factors like stage, gender and comorbidity, but also by lack of local and regional tumour control. Several studies examined pattern of failure in patients with oesophageal cancer treated with definitive chemoradiotherapy. Most patients experience local failure, and most local failures were located in the Gross Tumor volume (GTV). These findings imply that future therapeutic strategies should focus on improving local control in order to increase successful treatment outcome, although care should be taken to ensure that this does not come at the cost of excess treatment related toxicity.
Strategies to overcome in-GTV failures include radiotherapy-sensitizing agents and dose escalation, the latter has been evaluated in several studies with heterogeneous results.
The role of Positron Emissions Tomografi/ComputerTomografi (PET/CT) in radiotherapy planning has been examined and the diagnostic value of PET/CT in oesophageal cancer is widely accepted, whereas the role in assessing tumour response to treatment is less well established. Flour-Deoxy-Glucose (FDG)-PET scans allow for measurement of changes in tumour cell metabolism that precede changes in tumour size, and reduction in FDG uptake during neoadjuvant therapy has been correlated with favourable outcomes in patients with oesophageal cancer.
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
- •The patients must meet all of the following inclusion criteria to be included in the study:
- •Patients with histologically verified squamous cell or adenocarcinoma (including signet cell carcinoma) of the oesophagus or GEJ.
- •Multi-Disciplinary Team (MDT) assessment and treatment recommendation; deemed nonresectable and/or inoperable.
- •TNM stage (8th edition): cT1-4a or cN+, cM0-1 (M1 disease limited to metastatic lymph nodes)
- •Age ≥18 years.
- •Performance status ≤
- •Adequate cardiac, lung and renal function measured according to local guidelines.
- •Adequate laboratory findings:
- •haematological: haemoglobin > 90 g/L, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L
- •hepatic: bilirubin ≤ 1.5 x ULN, ALAT ≤ 3 x ULN
- •renal: creatinine ≤ 1.5 x ULN
- •Suitability to undergo curatively intended chemoradiation therapy.
- •Ability to adhere to procedures for study and follow-up.
- •Women must present a negative pregnancy test. Fertile men and women must use effective contraception. Fertile women included in the study must use oral contraceptives, intrauterine devices, depot injection of progestin subdermal implantation, a hormonal vaginal ring, or transdermal patch during the study treatment and one month after.
- •Signed informed consent to participate in the study, including acceptance that dose plan and scans will be stored in a national dose plan bank, and the remaining data stored in a central database.
- •A standard plan for radiotherapy with homogenous 50 Gy / 25 fractions, meeting all dose constraints for normal tissue, must be achievable.
排除标准
- •Patients who will meet one or more of the following exclusion criteria cannot be included in this study:
- •Prior oncological treatment or surgical resection for the present disease
- •Broncho-pulmonary fistula verified by bronchoscopy
- •Any other active malignancies which may compromise study protocol or endpoints except for basal or squamous cell skin cancer
- •Any unstable systemic disease (including clinically significant cardiovascular disease, unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart, severe hepatic, renal or metabolic disease or active inflammatory bowel disease)
- •Symptomatic peripheral neuropathy greater than grade 1 (CTCAE version 4.03)
- •Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial
- •Severely decreased lung function
结局指标
主要结局
Loco-regional control
时间窗: 12 months
Loco-regional control evaluated with Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG-PET)
次要结局
- Overall survival(1 and 5 years)
- Progression-free survival(1 and 5 years)
- Acute and late toxicity(5 years)
- Pattern of failure in CTV(5 years)
- Pattern of failure outside PTV(5 years)
- Stability of the FDG-PET signal, shape(12 months)
- Pattern of failure in GTV-T(5 years)
- Dose distributions(6 months)
- Correlation between loco-regional progression after treatment and changes in FDG-PET uptake pattern during standard and dose-escalated radiotherapy.(12 months)
- Treatment completion rate(12 months)
- Hospitalization(12 months)
- Mean and maximum dose distributions(6 months)
- Stability of the FDG-PET signal, intensity(12 months)
- Stability of the FDG-PET signal, heterogeniety(12 months)
- Pattern of failure in GTV-N(5 years)
- Pattern of failure in GTV-PET(5 years)
- Pattern of failure in PTV(5 years)