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
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
95
Cisplatin 75 mg/m2 IV (with adequate hydration) on D1 every 3 weeks.
500mg/m² IV(10 min. infusion, preceded by the usual folic acid, vitamin B12 and corticosteroid premedication)on D1 every 3 weeks
7.5 mg/kg on D1 every 3 weeks. In case of eligibility for Bevacizumab, the latter will not be started until C2.
Cerebral radiotherapy (encephalon in toto, 30 gy 10 sessions and 12 days) immediately after randomization before D1.If the number of brain metastases is less than or equal to 5 and less than or equal to 5 cm size, cerebral stereotactic radiotherapy condition may be proposed. The recommended interval between randomisation and D1 will be approximately 4 weeks.
Centre Hospitalier
Charleville-Mézières, Ardennes, France
Centre Hospitalier du Pays d'Aix
Aix-en-Provence, France
Centre Hospitalier Victor Dupouy
Argenteuil, France
Centre d'Oncologie et de Radiothérapie du Pays Basque
Bayonne, France
Centre Hospitalier
Beauvais, France
Hôpital Avicenne
To compare the progression-free survival rate in both arms
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.
Time frame: 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
Overall survival
After 4 cycles of chemotherapy with platinum salt-pemetrexed (with or without bevacizumab) possibly followed, in case of control of the disease and if the patient's condition allows, by pemetrexed (alone or with bevacizumab if the latter was part of the initial treatment) as maintenance treatment until progression.
Time frame: From the date of randomization until the date of patient death, assessed up to 90 months
Disease control rate (response + stability)
Repeat examinations to assess the measurable lesions or initials and examination necessary to confirm the appearance of a new lesion in case of clinical suspicion of disease progression (minimum CT scan and MRI).The radiological treatment response will be measured according to the RECIST 1.1 criteria
Time frame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
Tolerance of treatment
The safety of the induction combination of cisplatin or carboplatin plus pemetrexed (Alimta®) +/- bevacizumab, the maintenance treatment with pemetrexed (Alimta®) +/- bevacizumab and the pancerebral radiotherapy will be assessed based on the CTC toxicity criteria v3.0.
Time frame: Every 3 weeks, up to approximately 24 months
Quality of life assessment
The quality of life assessment measurement will be performed by self-questionnaire. The EURO-QOL questionnaire will be used.
Time frame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
Neurological assessment
The neurological assessment measurement will be performed by self-questionnaire. The MOCA questionnaires will be used.
Time frame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
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Bobigny, France
HIA de Clermont-Tonnerre
Brest, France
CHU
Brest, France
Centre François Baclesse
Caen, France
Centre Hospitalier Laennec
Creil, France
...and 31 more locations