Multicentric, Randomized, Phase III Trial Comparing 2 Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Asymptomatic Brain Metastases
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 95
- 试验地点
- 33
- 主要终点
- To compare the progression-free survival rate in both arms
研究概览
简要总结
The patients carrying a complicated primary lung cancer brain metastases die in less than 3 months of delay disease in the absence of treatment. The median survival of these patients is approximately six months when the treatment associated with radiotherapy chemotherapy based on cisplatin is now the standard treatment. In most studies the patients die of their brain disease in one case only two, so it is likely that some patients do not require brain irradiation (prognosis in this case is linked to extra-cerebral disease ). The benefits for patients in group B (without systematic irradiation) are not to suffer the side effects of this radiation. The risks are in the same group to see brain metastases become symptomatic.
The role of cerebral radiotherapy in the patients treated with chemotherapy is unclear: should all patients be irradiated systematically (since the "reference" treatment is involved and with the aim of obtaining better control of the brain lesions and maintaining a better neurological status) or should only the patients showing cerebral progression be irradiated (avoidance of possibly useless brain radiotherapy and its side effects). The aim of this study is to better determine the position of cerebral radiotherapy in this context.
Main objective:
determine whether there is a difference in terms of progression-free survival between a therapeutic strategy with initial systematic brain radiotherapy followed by chemotherapy cis-platine/alimta + / - Bevacizumab and strategy with an initial chemotherapy cis-platine/alimta + / - Bevacizumab associated with brain radiotherapy only in cases of cerebral progression in patients with NSCLC with asymptomatic brain metastases
详细描述
This is a trial comparing two strategies with the aim to determine the best place for cerebral radiotherapy (initially or only systematic progression).
Arm A: Initial cerebral radiotherapy and chemotherapy, standard arm Arm B: Chemotherapy and Radiotherapy brain if clinical or radiological cerebral progression , experimental arm (The chemotherapy treatments are standard treatments using drugs with authorization in this indication)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Patients with histologically or cytologically proven non-epidermoid, non-small cell lung cancer, non-EGFR (Epidermal Growth Factor Receptor)-mutated (or mutation test impracticable).
- •Patients with brain metastasis/metastases without neurosurgical indication.
- •Asymptomatic patients (without treatment or with stable steroids or antiepileptic treatments for ≥ 5 days prior to obtaining the baseline MRI of the brain, and ≥ 5 days prior to first dose of study treatment (Cycle 1, Day 1).
- •At least one lesion measurable according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.
- •ECOG (Eastern Cooperative Oncology Group) Performance Status 0 - 1
- •No previous chemotherapy for this cancer, apart from adjunctive chemotherapy more than 18 months ago.
- •Prior surgery is authorized in case of documented recurrence or progression.
- •Adequate biological functions (hematologic, platelets, hemoglobin, hepatic function, alkaline phosphatases, ASAT (Aspartate transaminase) and ALAT (Alanine Aminotransferase); creatinine clearance).
- •For women: Effective contraception for women of childbearing age during treatment and for 6 months following treatment.
- •For men: They must be surgically sterile or accept the use of effective contraception until 6 months after the treatment period.
- •Patients of more than 18 years of age.
- •Estimated survival of at least 12 weeks.
- •Consent signed by the patient
排除标准
- •Patients presenting with a brain lesion eligible for curative treatment (neurosurgical).
- •Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
- •Epidermoid carcinoma.
- •Con indication of Bevacizumab is furthermore
- •Patients presenting with a brain lesion eligible for curative treatment (neurosurgery or radiosurgery).
- •Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
- •Epidermoid carcinoma.
- •Cons indication of Bevacizumab
- •Inability to take the folic acid or vitamin B12 vitamin supplementation or the dexamethasone premedication (or any equivalent corticosteroid), or any inability to comply with the study procedures.
- •History of cancer, with the exception of cervical cancer in situ, skin cancer other than melanoma, adequately treated low-grade prostatic cancer (Gleason score <6), unless this cancer was diagnosed and treated more than 5 years ago without any signs of recurrence.
- •Patients presenting with a systemic disorder which, in the investigator's opinion, compromises their participation in the study for reasons related to treatment safety or compliance.
- •Patients incapable of discontinuing their aspirin treatment when the dose is > 1300 mg/day or their non-steroidal anti-inflammatory treatment two days before the day, on the day and two days the day of administration of pemetrexed (Alimta).
- •Patients presenting with a 3rd sector (pleural effusion, ascites) which is clinically detectable and uncontrollable by simple measures of the evacuatory puncture type or other treatment before inclusion in the study.
- •Patients presenting with neuropathy of grade > 2 according to the criteria of CTC (Common toxicity Criteria) v3.
- •Patients whose foreseeable compliance or geographical distance renders monitoring difficult.
- •Pregnant or breast-feeding women.
- •Significant weight loss (≥ 10%) during the 6 weeks preceding inclusion in the study.
- •Vaccination against yellow fever within 30 days preceding inclusion in the study.
- •Cons-indication to taking steroids
- •Persons deprived of their liberty as a result of a judicial or administrative decision
- •Concomitant participation in another trial
研究组 & 干预措施
Arm A (standard arm)
Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)
干预措施: Cisplatin (Drug)
Arm A (standard arm)
Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)
干预措施: Pemetrexed (Drug)
Arm A (standard arm)
Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)
干预措施: Bevacizumab (Drug)
Arm A (standard arm)
Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)
干预措施: Cerebral Radiotherapy (Radiation)
Arm B (experimental arm)
Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain
干预措施: Cisplatin (Drug)
Arm B (experimental arm)
Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain
干预措施: Pemetrexed (Drug)
Arm B (experimental arm)
Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain
干预措施: Bevacizumab (Drug)
Arm B (experimental arm)
Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain
干预措施: Cerebral Radiotherapy (Radiation)
结局指标
主要结局
To compare the progression-free survival rate in both arms
时间窗: From date of the randomization until the date of first detection of progression, or until the date of death, assessed up to up to approximately 90 months
Whether there is a difference in terms of progression-free survival between a therapeutic strategy with initial brain radiotherapy followed by systematic chemotherapy with cis-platinum / alimta and a strategy with initial chemotherapy with cis-platinum / alimta with brain radiotherapy only if brain progression in patients with non-small cell lung cancer with brain metastases asymptomatic.
次要结局
- Overall survival(From the date of randomization until the date of patient death, assessed up to 90 months)
- Disease control rate (response + stability)(Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months)
- Tolerance of treatment(Every 3 weeks, up to approximately 24 months)
- Quality of life assessment(Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months)
- Neurological assessment(Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months)
研究者
Isabelle MONNET
Physician
Centre Hospitalier Intercommunal Creteil