Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Brain Metastases

NCT02162537 | Terminated Phase 3 DMC

• 1 other identifier: METAL 2
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 41

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

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• 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

Study Arms (2)

Arm A (standard arm)

OTHER

Arm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)

Drug: Cisplatin; Drug: Pemetrexed; Drug: Bevacizumab; Radiation: Cerebral Radiotherapy

Arm B (experimental arm)

OTHER

Arm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain

Drug: Cisplatin; Drug: Pemetrexed; Drug: Bevacizumab; Radiation: Cerebral Radiotherapy

Interventions

Cisplatin DRUG

Cisplatin 75 mg/m2 IV (with adequate hydration) on D1 every 3 weeks.

Also known as: Cisplatine

Arm A (standard arm); Arm B (experimental arm)

Pemetrexed DRUG

500mg/m² IV(10 min. infusion, preceded by the usual folic acid, vitamin B12 and corticosteroid premedication)on D1 every 3 weeks

Also known as: Alimta

Arm A (standard arm); Arm B (experimental arm)

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.

Also known as: Avastin

Arm A (standard arm); Arm B (experimental arm)

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.

Also known as: Brain Radiotherapy

Arm A (standard arm); Arm B (experimental arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 neuropathy of grade \> 2 according to the criteria of CTC (Common toxicity Criteria) v3.0.
• Patients whose foreseeable compliance or geographical distance renders monitoring difficult.
• Pregnant or breast-feeding women.

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• Groupe Francais De Pneumo-Cancerologie: collaborator

Study Sites (41)

Centre Hospitalier

Charleville-Mézières, Ardennes, 08000, France

Location

Centre Hospitalier du Pays d'Aix

Aix-en-Provence, 13613, France

Location

Centre Hospitalier Victor Dupouy

Argenteuil, 95100, France

Location

Centre d'Oncologie et de Radiothérapie du Pays Basque

Bayonne, 64100, France

Location

Centre Hospitalier

Beauvais, 60021, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

HIA de Clermont-Tonnerre

Brest, 22240, France

Location

CHU

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Hospitalier Laennec

Creil, 60109, France

Location

Centre Hospitalier Intercommunal

Créteil, 94010, France

Location

Centre Hospitalier

Draguignan, 83300, France

Location

Centre Hospitalier

Gap, 05000, France

Location

Centre Hospitalier Robert Boulin

Libourne, 33500, France

Location

Hôpital Le Cluzeau

Limoges, 87042, France

Location

Centre Hospitalier Régional

Longjumeau, 91161, France

Location

Centre Hospitalier de Bretagne Sud

Lorient, 56322, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Centre Hospitalier F. QUESNAY

Mantes-la-Jolie, 78200, France

Location

Institut Paoli Calmette

Marseille, 13000, France

Location

Hôpital Nord APHM

Marseille, 13915, France

Location

Centre Hospitalier Les Chanaux

Mâcon, 71000, France

Location

Centre Hospitalier

Meaux, 77108, France

Location

Centre Hospitalier Intercommunal

Meulan-en-Yvelines, 78250, France

Location

Clinique du Pont de Chaume

Montauban, 82000, France

Location

Centre Catalan d'Oncologie

Perpignan, 66000, France

Location

Centre Hospitalier

Périgueux, 24019, France

Location

Centre Hospitalier René Dubos

Pontoise, 95303, France

Location

Centre Hospitalier de la Région d'Annecy (CHRA)

Pringy, 74374, France

Location

Centre Hospitalier Intercommunal de Cornouaille

Quimper, 29107, France

Location

Hôpital Pontchailloux

Rennes, 35033, France

Location

Hôpital Charles Nicolle

Rouen, 79031, France

Location

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, 44600, France

Location

Institut de Cancérologie de la Loire (I.C.L)

Saint-Priest-en-Jarez, 42271, France

Location

Centre Hospitalier de Salon de Provence

Salon-de-Provence, 13658, France

Location

Centre Hospitalier

Sens, 89108, France

Location

Centre Paul Strauss

Strasbourg, 67000, France

Location

Hopital d'Instruction des Armées Sainte Anne

Toulon, 83800, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

Centre Hospitalier

Villefranche-sur-Saône, 69655, France

Location

Related Publications (1)

• 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.

  PMID: 33948123 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Pemetrexed; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Isabelle MONNET

  Centre Hospitalier Intercommunal Créteil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: June 12, 2014
• Study Start: December 1, 2013
• Primary Completion: March 1, 2018
• Study Completion: January 1, 2019
• Last Updated: February 1, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (41)