Randomized Open Phase II Multienter Study Evaluating the Clinical Utility of Online Adaptive Radiotherapy in Bladder Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 120
- 试验地点
- 22
- 主要终点
- evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity.
研究概览
简要总结
Trimodal therapy (TMT) consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy is a therapeutic alternative in patients with Muscle-Infiltrating Bladder Cancer who are inoperable or refuse surgery. One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during and between radiotherapy sessions. Standard radiotherapy techniques require large planning target volume margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities.
Adaptive radiotherapy allows for the generation of a treatment fraction personalized to a patient's anatomical modification with margin reduction and improves the dosimetric quality of the delivered plans.
The hypothesis is that this improvement results in radiation-induced toxicity improvement.
详细描述
In 2023, the incidence of muscle-infiltrating bladder cancer (MIBC) in France was 14062 cases, 81% of which were in men.
The standard treatment for MIBC is cystectomy preceded by neoadjuvant chemotherapy. Trimodal therapy (TMT), consisting of transurethral resection of bladder tumors (TURBT) followed by radiotherapy (RT) and chemotherapy (CT), has emerged as a valuable therapeutic de-escalation alternative in patients who are inoperable or refuse surgery with its physical and psychological sequelae. TMT provides survival outcomes identical to cystectomy in selected patients and allows for bladder preservation in successful cases. TMT is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder who failed intravesical therapy.
One of the main challenges of TMT is the planning and delivery of radiation therapy. Indeed, the bladder is a mobile hollow organ subject to repletion, with variations in size and shape during radiotherapy sessions (intra-fractional movement) and between sessions (inter-fractional movement). To take into account these movements, standard radiotherapy techniques require large planning target volume (PTV) margins around the bladder, which can be responsible for irradiation of a large volume of large and small bowel with grade 2 and 3 toxicities up to 42% and 17% respectively.
Adaptive radiotherapy (ART) allows for the generation of a treatment fraction personalized to a patient's anatomical modification. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible to perform a daily customization of the radiotherapy session ("online") for a given patient to ensure optimal coverage of the target with minimized margins. ART allows PTV margins reduction for MIBC and improves therefore the dosimetric quality of the delivered plans.
The hypothesis is that the dosimetric improvement induced by ART results in radiation-induced toxicity improvement.
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
- •Histologically proven muscle-infiltrating bladder cancer (de novo MIBC or after a history of non-muscle-invasive bladder cancer) or patients with initial high-grade T1 tumor showing Ta or T1 recurrence, or those with high-grade T1 after a course of intravesical biological therapy or chemotherapy;
- •Age ≥ 18 years;
- •Urothelial carcinoma (transitional cell carcinoma of the bladder, micropapillary, microcystic with trophoblastic differenciation) and squamous cell histological types are allowed;
- •Stage T1-T4aN0M0
- •TransUrethral Resection of Bladder Tumor (TURBT) and Position Emission Tomography- scanner and X-ray Computed Tomography (PET-CT) or Computed Tomography scan of thorax/abdomen/pelvis (without carcinological anomaly) within 8 weeks prior to the start of radiation therapy (if TURBT was performed more than 6 weeks before the inclusion visit, a new TURBT or, at least, a cystoscopy showing no progression, no residual tumour or regrowth must be done);
- •Suitable for radiotherapy;
- •Eastern Cooperative Oncology Group/World Human Organisation (ECOG/WHO) performance status from 0 to 2
- •Negative pregnancy test (blood or urine), for women of childbearing age only;
- •If the patient is sexually active, he/she must agree to use contraception deemed adequate and appropriate by the investigator throughout the period of study drug administration and 6 months after the end of treatment for both men and women.
- •Affiliation to the French Social Security System;
- •Dated, written and signed Informed consent
排除标准
- •Prior pelvic radiation therapy;
- •Patients with previous or concomitant other malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years;
- •Presence of endopenic stent;
- •Inability to comply with the protocol;
- •Grade 1 or greater baseline diarrhea;
- •Uncontrolled inflammatory bowel disease (ulcerative colitis or Crohn's disease);
- •Uncontrolled immune or cardiac or pulmonary disease;
- •Patients whose regular follow-up is impossible for psychological, family, social or geographical reasons;
- •Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study;
- •Pregnant or breast-feeding subjects
结局指标
主要结局
evaluation of the technique of adaptive radiotherapy in terms of acute Gastro-Intestinal toxicity.
时间窗: from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy
rate of patients without acute diarrhea grade ≥2
次要结局
- Evaluation of all acute toxicities(from the Day 1 Radiotherapy to 3 months after the last day of Radiotherapy)
- Evaluation of all late toxicities(from 3 months after the last day of Radiotherapy to 5 years after the last day of Radiotherapy)
- evaluation of quality of life specific to the cancer disease(at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.)
- evaluation of quality of life and of the measurements specific to the treatment of bladder cancer with muscle invasion(at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.)
- evaluation of quality of life for patient ≥ 70 years old in order to establish a minimum standardized geriatric assessment(at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.)
- evaluation of quality of life for patient ≥ 70 years old (Specific to elderly people with cancer)(at baseline, the last day of radiotherapy, every 3 months after the last day of radiotherapy, during first year and every 6 months then after until 3 years.)
- assessment of disease free survival(At 3 and 5 years after the last day of Radiotherapy)
- assessment of cystectomy free survival(At 3 and 5 years after the last day of Radiotherapy)
- assessment of overall survival(At 3 and 5 years after the last day of Radiotherapy)
- assessment of local control rate(At 3 and 5 years after the last day of Radiotherapy)
- assessment of the dosimetric results(during tthe radiotherapy for both arms)
- evaluation of the impact of the adaptive process on fractions execution(during tthe radiotherapy for both arms)