Clinical trial NCT02162537: Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Brain Metastases
Official title: Multicentric, Randomized, Phase III Trial Comparing 2 Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Asymptomatic Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer Metastatic
Non-small Cell Lung Cancer
Adenocarcinoma of Lung Metastatic to Brain
Cerebral Metastases
Keywords: Strategy
Radiotherapy
Chemotherapy
Cisplatin
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
Collaborators: name: Groupe Francais De Pneumo-Cancerologie
First posted: 2014-06-12
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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

Detailed description: 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)

Eligibility criteria: Inclusion Criteria:

1. Patients with histologically or cytologically proven non-epidermoid, non-small cell lung cancer, non-EGFR (Epidermal Growth Factor Receptor)-mutated (or mutation test impracticable).
2. Patients with brain metastasis/metastases without neurosurgical indication.
3. 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).
4. At least one lesion measurable according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.
5. ECOG (Eastern Cooperative Oncology Group) Performance Status 0 - 1
6. No previous chemotherapy for this cancer, apart from adjunctive chemotherapy more than 18 months ago.
7. Prior surgery is authorized in case of documented recurrence or progression.
8. Adequate biological functions (hematologic, platelets, hemoglobin, hepatic function, alkaline phosphatases, ASAT (Aspartate transaminase) and ALAT (Alanine Aminotransferase); creatinine clearance).
9. 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.
10. Patients of more than 18 years of age.
11. Estimated survival of at least 12 weeks.
12. Consent signed by the patient

Exclusion Criteria:

1. Patients presenting with a brain lesion eligible for curative treatment (neurosurgical).
2. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
3. Epidermoid carcinoma.
4. Con indication of Bevacizumab is furthermore
5. Patients presenting with a brain lesion eligible for curative treatment (neurosurgery or radiosurgery).
6. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.
7. Epidermoid carcinoma.
8. Cons indication of Bevacizumab
9. 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.
10. 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.
11. 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.
12. 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).
13. 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.
14. Patients presenting with neuropathy of grade \> 2 according to the criteria of CTC (Common toxicity Criteria) v3.0.
15. Patients whose foreseeable compliance or geographical distance renders monitoring difficult.
16. Pregnant or breast-feeding women.
17. Significant weight loss (≥ 10%) during the 6 weeks preceding inclusion in the study.
18. Vaccination against yellow fever within 30 days preceding inclusion in the study.
19. Cons-indication to taking steroids
20. Persons deprived of their liberty as a result of a judicial or administrative decision
21. Concomitant participation in another trial

Primary outcomes:
measure: To compare the progression-free survival rate in both arms
timeFrame: 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
Secondary outcomes:
measure: Overall survival
timeFrame: From the date of randomization until the date of patient death, assessed up to 90 months
measure: Disease control rate (response + stability)
timeFrame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
measure: Tolerance of treatment
timeFrame: Every 3 weeks, up to approximately 24 months
measure: Quality of life assessment
timeFrame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
measure: Neurological assessment
timeFrame: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months
Other outcomes:
Locations:
city: Charleville-Mézières
country: France
facility: Centre Hospitalier
state: Ardennes
city: Aix En Provence
country: France
facility: Centre Hospitalier du Pays d'Aix
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy
city: Bayonne
country: France
facility: Centre d'Oncologie et de Radiothérapie du Pays Basque
city: Beauvais
country: France
facility: Centre Hospitalier
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Brest
country: France
facility: HIA de Clermont-Tonnerre
city: Brest
country: France
facility: CHU
city: Caen
country: France
facility: Centre François Baclesse
city: Creil
country: France
facility: Centre Hospitalier Laennec
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal
city: Draguignan
country: France
facility: Centre Hospitalier
city: GAP
country: France
facility: Centre Hospitalier
city: Libourne
country: France
facility: Centre Hospitalier Robert Boulin
city: Limoges
country: France
facility: Hôpital Le Cluzeau
city: Longjumeau
country: France
facility: Centre Hospitalier Régional
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud
city: Lyon
country: France
facility: Centre Léon Bérard
city: Macon
country: France
facility: Centre Hospitalier Les Chanaux
city: Mantes La Jolie
country: France
facility: Centre Hospitalier F. QUESNAY
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Marseille
country: France
facility: Hôpital Nord APHM
city: Meaux
country: France
facility: Centre Hospitalier
city: Meulan-en-Yvelines
country: France
facility: Centre Hospitalier Intercommunal
city: Montauban
country: France
facility: Clinique du Pont de Chaume
city: Perigueux
country: France
facility: Centre Hospitalier
city: Perpignan
country: France
facility: Centre Catalan d'Oncologie
city: Pontoise
country: France
facility: Centre Hospitalier René Dubos
city: Pringy
country: France
facility: Centre Hospitalier de la Région d'Annecy (CHRA)
city: Quimper
country: France
facility: Centre Hospitalier Intercommunal de Cornouaille
city: Rennes
country: France
facility: Hôpital Pontchailloux
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint Nazaire
country: France
facility: Clinique Mutualiste de l'Estuaire
city: Saint Priest En Jarez
country: France
facility: Institut de Cancérologie de la Loire (I.C.L)
city: Salon de Provence
country: France
facility: Centre Hospitalier de Salon de Provence
city: Sens
country: France
facility: Centre Hospitalier
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulon
country: France
facility: Hopital d'Instruction des Armées Sainte Anne
city: Toulouse
country: France
facility: Hôpital Larrey
city: Toulouse
country: France
facility: Clinique Pasteur
city: Villefranche Sur Saone
country: France
facility: Centre Hospitalier
Study officials:
affiliation: Centre Hospitalier Intercommunal Créteil
name: Isabelle MONNET
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.