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Non-small Cell Lung Cancer MetastaticPhase 3METAL2NCT02162537

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

A Phase 3 study testing Cisplatin, Pemetrexed and Bevacizumab in people with Non-small Cell Lung Cancer Metastatic and Non-small Cell Lung Cancer, run by Centre Hospitalier Intercommunal Creteil at 41 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cisplatin, Pemetrexed and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
41 sitesFrance
Study dates
Dec 2013to Jan 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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) v3.0.
  • 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

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

France41 sites

  • Centre Hospitalier du Pays d'Aix

    Aix-en-Provence, 13613

  • Centre Hospitalier Victor Dupouy

    Argenteuil, 95100

  • Centre d'Oncologie et de Radiothérapie du Pays Basque

    Bayonne, 64100

  • Centre Hospitalier

    Beauvais, 60021

  • Hôpital Avicenne

    Bobigny, 93000

  • HIA de Clermont-Tonnerre

    Brest, 22240

  • CHU

    Brest, 29200

  • Centre François Baclesse

    Caen, 14000

  • Centre Hospitalier

    Charleville-Mézières, Ardennes, 08000

  • Centre Hospitalier Laennec

    Creil, 60109

  • Centre Hospitalier Intercommunal

    Créteil, 94010

  • Centre Hospitalier

    Draguignan, 83300

  • Centre Hospitalier

    Gap, 05000

  • Centre Hospitalier Robert Boulin

    Libourne, 33500

  • Hôpital Le Cluzeau

    Limoges, 87042

  • Centre Hospitalier Régional

    Longjumeau, 91161

  • Centre Hospitalier de Bretagne Sud

    Lorient, 56322

  • Centre Léon Bérard

    Lyon, 69373

  • Centre Hospitalier Les Chanaux

    Mâcon, 71000

  • Centre Hospitalier F. QUESNAY

    Mantes-la-Jolie, 78200

  • Institut Paoli Calmette

    Marseille, 13000

  • Hôpital Nord APHM

    Marseille, 13915

  • Centre Hospitalier

    Meaux, 77108

  • Centre Hospitalier Intercommunal

    Meulan-en-Yvelines, 78250

  • Clinique du Pont de Chaume

    Montauban, 82000

  • Centre Hospitalier

    Périgueux, 24019

  • Centre Catalan d'Oncologie

    Perpignan, 66000

  • Centre Hospitalier René Dubos

    Pontoise, 95303

  • Centre Hospitalier de la Région d'Annecy (CHRA)

    Pringy, 74374

  • Centre Hospitalier Intercommunal de Cornouaille

    Quimper, 29107

  • Hôpital Pontchailloux

    Rennes, 35033

  • Hôpital Charles Nicolle

    Rouen, 79031

  • Clinique Mutualiste de l'Estuaire

    Saint-Nazaire, 44600

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

    Saint-Priest-en-Jarez, 42271

  • Centre Hospitalier de Salon de Provence

    Salon-de-Provence, 13658

  • Centre Hospitalier

    Sens, 89108

  • Centre Paul Strauss

    Strasbourg, 67000

  • Hopital d'Instruction des Armées Sainte Anne

    Toulon, 83800

  • Hôpital Larrey

    Toulouse, 31059

  • Clinique Pasteur

    Toulouse, 31076

  • Centre Hospitalier

    Villefranche-sur-Saône, 69655

Other trials in France

About this study

Official title: Multicentric, Randomized, Phase III Trial Comparing 2 Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Asymptomatic Brain Metastases

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.

Read more

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

Read the 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)

Being tested
Cisplatin, Pemetrexed, Bevacizumab, Cerebral Radiotherapy
Keywords
Strategy, Radiotherapy, Chemotherapy, Cisplatin
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Cisplatine

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

  • PemetrexedDrug

    Also called Alimta

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

  • BevacizumabDrug

    Also called Avastin

    7.5 mg/kg on D1 every 3 weeks. In case of eligibility for Bevacizumab, the latter will not be started until C2.

  • Cerebral RadiotherapyRadiation

    Also called Brain Radiotherapy

    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.

Study groups in NCT02162537
Study groupRoleWhat they receive
Arm A (standard arm)OtherArm A: Initial Cerebral Radiotherapy and Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab)
Receives: Drug: Cisplatin; Drug: Pemetrexed; Drug: Bevacizumab; Radiation: Cerebral Radiotherapy
Arm B (experimental arm)OtherArm B: Chemotherapy (Cisplatin and pemetrexed with or without Bevacizumab) and Cerebral Radiotherapy if clinical or radiological progression brain
Receives: Drug: Cisplatin; Drug: Pemetrexed; Drug: Bevacizumab; Radiation: Cerebral Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

    Measured: From the date of randomization until the date of patient death, assessed up to 90 months

  2. 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

    Measured: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months

  3. 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.

    Measured: Every 3 weeks, up to approximately 24 months

  4. Quality of life assessment

    The quality of life assessment measurement will be performed by self-questionnaire. The EURO-QOL questionnaire will be used.

    Measured: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months

  5. Neurological assessment

    The neurological assessment measurement will be performed by self-questionnaire. The MOCA questionnaires will be used.

    Measured: Baseline, between 21 and 28 days, then every 6 weeks, up to approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2014 (estimated)
  2. Study startDec 2013
  3. Primary completionMar 2018
  4. Study completionJan 2019

Why it stopped: Slow inclusions due in part to a change in practices. The first chemotherapy become a standard for patients with NSCL with asymptomatic brain metastases.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02162537
Sponsor's protocol ID
METAL 2
Acronym
METAL2
Status last verified
Jan 2019
First submitted
21 Mar 2014
Last updated
1 Feb 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 33948123

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cisplatin, Pemetrexed and Bevacizumab in people with Non-small Cell Lung Cancer Metastatic and Non-small Cell Lung Cancer, run by Centre Hospitalier Intercommunal Creteil at 41 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow inclusions due in part to a change in practices. The first chemotherapy become a standard for patients with NSCL with asymptomatic brain metastases.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To compare the progression-free survival rate in both arms (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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02162537, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.

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