Evaluation of the Stereotactic MR-guided Adaptive Radiotherapy for Locally Advanced Pancreatic Cancers
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 试验地点
- 34
- 主要终点
- Improvement of local control at 1 year by 20% in the experimental cohort compared with the standard cohort.
研究概览
简要总结
Pancreatic cancer is on the rise, and is set to become the 2nd leading cause of cancer deaths by 2030. Its prognosis is very poor, with a 5-year survival rate of just 5.5%. Curative surgery with chemotherapy improves survival, but only 20% of patients are eligible. For locally advanced forms, radiotherapy, notably in the form of MRI-guided adaptive stereotactic radiotherapy (SMART), is showing promising results in terms of survival and local control, but still requires prospective validation.
详细描述
In 2016, pancreatic cancer became the 3rd leading cause of cancer death worldwide, and could be the 2nd by 2030. Its prognosis remains very unfavorable, with a 5-year overall survival rate of 5.5%, all stages combined. In France, incidence is on the rise, with 14,100 new cases and 11,400 deaths in 2018. The only therapeutic strategy that has shown a significant improvement in survival is curative surgery followed by adjuvant chemotherapy, but only 20% of patients are eligible. The majority of cases are diagnosed at an advanced or unresectable stage.
For locally advanced cancers (LACC), management is not standardized. Two induction chemotherapy regimens have been validated: FOLFIRINOX and GEMBRAX. The role of radiochemotherapy remains debated. The LAP07 study showed no significant benefit of radiochemotherapy on overall survival, although it did improve progression-free survival and locoregional control.
New techniques such as MRI-guided adaptive stereotactic radiotherapy (SMART) enable more targeted and intense delivery of radiation dose, while protecting organs at risk. Retrospective studies have shown a significant improvement in local control (up to 98% at 1 year) and overall survival (up to 23 months) with this method, compared with conventional radiotherapy. However, prospective studies are still needed to confirm the value of SMART in the management of locally advanced pancreatic 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
- •Histologically proven pancreatic adenocarcinoma ;
- •Age ≥ 18 years ;
- •WHO score 0-1 ;
- •Locally advanced according to NCCN 1.2015 recommendations;
- •Non-metastatic after TAP scan and MRI of the liver ;
- •CA 19.9 < 1000 IU/mL ;
- •Completion of at least 4 cycles of induction chemotherapy (Folfirinox and/or Gemzar-Abraxane) with a maximum of 8 courses ;
- •Women of childbearing potential must have a pregnancy blood test within a maximum of 7 days before starting the study treatment. A negative result must be documented before study treatment is started. Women without reproductive potential are postmenopausal women or women who have undergone permanent sterilisation (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) ;
- •Effective contraception for women of childbearing age ;
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures ;
- •Patient has given informed, written and express consent ;
- •Patient affiliated to a French health insurance scheme.
排除标准
- •Other concomitant cancer or history of cancer, with the exception of treated cervical cancer in situ, basal or squamous cell skin carcinoma, superficial bladder tumour (Ta, Tis, and T1) or a tumour with a good prognosis treated curatively without chemotherapy and without evidence of disease in the 3 years prior to inclusion ;
- •History of radiotherapy with a foreseeable overlap with the radiotherapy treatment under study (history of abdominal irradiation) ;
- •Contraindication to MRI and MRI-guided radiotherapy (claustrophobia, presence of metallic elements etc...) ;
- •History of chronic inflammatory disease of the colon or rectum ;
- •Women who are pregnant, parturient or breastfeeding ;
- •Any other serious concomitant and unbalanced disease or disorder that may interfere with the patient's participation in the study and his/her safety during the study (e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders) ;
- •Legal incapacity (patient under curatorship or guardianship) ;
- •History of severe and unexpected reactions to treatment containing a fluoropyrimidine ;
- •Hypersensitivity to capecitabine, to used excipients or to fluorouracil ;
- •Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) ;
- •In patients with severe leukopenia, neutropenia or thrombocytopenia ;
- •In patients with severe hepatic insufficiency ;
- •Patients with severe renal insufficiency (creatinine clearance less than 30 mL/min) ;
- •Recent or concomitant treatment with brivudine.
结局指标
主要结局
Improvement of local control at 1 year by 20% in the experimental cohort compared with the standard cohort.
时间窗: From enrollment to one year after treatment completion
Local control rate, assessed by TAP scan according to RECIST 1.1 criteria (Appendix 8) +/- oesogastroduodenal fibroscopy (FOGD) in case of upper digestive symptomatology not explained by CT scan. The local control rate is defined as the proportion of patients without local progression, the time to local progression being defined as the time between the start date of radiotherapy and the date of documented local progression. Patients will be censored at date of death if they die of a carcinological outcome other than local recurrence, or of another cause. Patients without local progression will be censored at the date of last follow-up.
次要结局
- Dosimetric benefits of daily adaptation, for each dosimetric parameter (GTV and PTV coverage, organs at risk doses), by comparing the average results obtained for each patient over all sessions with the 'adapted' plan compared to the 'predicted plan'(At the end of the treatment)
- Correlation between dosimetry and outcomes (local control, toxicities)(At the end of the treatment)
- Evaluation of Overall Survival(1 year after enrollment)
- Evaluation of progression-free survival(1 year after enrollment)
- Evaluation of Metastasis-free survival(1 year after enrollment)
- Evaluation of severe acute gastrointestinal toxicity(90 days after the end of radiotherapy)
- Evaluation of safety (acute and late toxicities of RT)(Up to 5 years after treatment)
- Quality of life evaluation(Up to 5 years after treatment)
- Evaluation of the evolution of the tumour marker CA 19.9(Until the end of the follow-up)
- Dosimetric benefits of daily adaptation, for each dosimetric parameter (GTV and PTV coverage, organs at risk doses), by comparing the average results obtained for each patient over all sessions with the 'adapted' plan compared to the 'predicted plan'(At the end of the treatment)
- Correlation between dosimetry and outcomes (local control, toxicities)(At the end of the treatment)