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Slow inclusions due in part to a change in practices. The first chemotherapy become a standard for patients with NSCL with asymptomatic brain metastases.
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| Name | Class |
|---|---|
| Groupe Francais De Pneumo-Cancerologie | OTHER |
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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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (standard arm) | Other | Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) |
|
| Arm B (experimental arm) | Other | Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin | Drug | Cisplatin 75 mg/m2 IV (with adequate hydration) on D1 every 3 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From the date of randomization until the date of patient death, assessed up to 90 months |
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Inclusion Criteria:
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Isabelle MONNET | Centre Hospitalier Intercommunal Créteil | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier | Charleville-Mézières | Ardennes | 08000 | France | ||
| Centre Hospitalier du Pays d'Aix |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33948123 | Derived | Monnet I, Vergnenegre A, Robinet G, Berard H, Lamy R, Falchero L, Vieillot S, Schott R, Ricordel C, Chouabe S, Thomas P, Gervais R, Madroszyk A, Abdiche S, Chiappa AM, Greillier L, Decroisette C, Auliac JB, Chouaid C; GFPC 02-13 (METAL2) investigators. Phase III randomized study of carboplatin pemetrexed with or without bevacizumab with initial versus "at progression" cerebral radiotherapy in advanced non squamous non-small cell lung cancer with asymptomatic brain metastasis. Ther Adv Med Oncol. 2021 Apr 16;13:17588359211006983. doi: 10.1177/17588359211006983. eCollection 2021. |
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| Pemetrexed | Drug | 500mg/m² IV(10 min. infusion, preceded by the usual folic acid, vitamin B12 and corticosteroid premedication)on D1 every 3 weeks |
|
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| Bevacizumab | Drug | 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 | Radiation | 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. |
|
|
| 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 | 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. | 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. | 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. | Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months |
| Aix-en-Provence |
| 13613 |
| France |
| Centre Hospitalier Victor Dupouy | Argenteuil | 95100 | France |
| Centre d'Oncologie et de Radiothérapie du Pays Basque | Bayonne | 64100 | France |
| Centre Hospitalier | Beauvais | 60021 | France |
| Hôpital Avicenne | Bobigny | 93000 | France |
| HIA de Clermont-Tonnerre | Brest | 22240 | France |
| CHU | Brest | 29200 | France |
| Centre François Baclesse | Caen | 14000 | France |
| Centre Hospitalier Laennec | Creil | 60109 | France |
| Centre Hospitalier Intercommunal | Créteil | 94010 | France |
| Centre Hospitalier | Draguignan | 83300 | France |
| Centre Hospitalier | Gap | 05000 | France |
| Centre Hospitalier Robert Boulin | Libourne | 33500 | France |
| Hôpital Le Cluzeau | Limoges | 87042 | France |
| Centre Hospitalier Régional | Longjumeau | 91161 | France |
| Centre Hospitalier de Bretagne Sud | Lorient | 56322 | France |
| Centre Léon Bérard | Lyon | 69373 | France |
| Centre Hospitalier F. QUESNAY | Mantes-la-Jolie | 78200 | France |
| Institut Paoli Calmette | Marseille | 13000 | France |
| Hôpital Nord APHM | Marseille | 13915 | France |
| Centre Hospitalier Les Chanaux | Mâcon | 71000 | France |
| Centre Hospitalier | Meaux | 77108 | France |
| Centre Hospitalier Intercommunal | Meulan-en-Yvelines | 78250 | France |
| Clinique du Pont de Chaume | Montauban | 82000 | France |
| Centre Catalan d'Oncologie | Perpignan | 66000 | France |
| Centre Hospitalier | Périgueux | 24019 | France |
| Centre Hospitalier René Dubos | Pontoise | 95303 | France |
| Centre Hospitalier de la Région d'Annecy (CHRA) | Pringy | 74374 | France |
| Centre Hospitalier Intercommunal de Cornouaille | Quimper | 29107 | France |
| Hôpital Pontchailloux | Rennes | 35033 | France |
| Hôpital Charles Nicolle | Rouen | 79031 | France |
| Clinique Mutualiste de l'Estuaire | Saint-Nazaire | 44600 | France |
| Institut de Cancérologie de la Loire (I.C.L) | Saint-Priest-en-Jarez | 42271 | France |
| Centre Hospitalier de Salon de Provence | Salon-de-Provence | 13658 | France |
| Centre Hospitalier | Sens | 89108 | France |
| Centre Paul Strauss | Strasbourg | 67000 | France |
| Hopital d'Instruction des Armées Sainte Anne | Toulon | 83800 | France |
| Hôpital Larrey | Toulouse | 31059 | France |
| Clinique Pasteur | Toulouse | 31076 | France |
| Centre Hospitalier | Villefranche-sur-Saône | 69655 | France |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D000068437 | Pemetrexed |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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