Carcinoma, Non-Small-Cell LungPhase 2METROSNCT02499614
Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
A Phase 2 study testing Crizotinib in people with Carcinoma, Non-Small-Cell Lung, run by Fondazione Ricerca Traslazionale at 26 sites in Italy.
Trial summary
Phase II, two arms, parallel, non comparative study with crizotinib in patients with ROS 1 translocation or MET amplification or MET exon 14 mutation Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Crizotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 26 sitesItaly
- Study dates
- Dec 2014to Dec 2018
- Phase
- Phase 2
- 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
- Histologically confirmed diagnosis of NSCLC
- Availability of tumor tissue for ROS1 and MET analyses
- Patient positive for ROS1 translocation or MET amplification
- At least one radiological measurable disease according to RECIST criteria (Response Evaluation Criteria in Solid Tumors )
- At least 1 previous standard chemotherapy regimen
- Performance status 0-2 (ECOG)
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- Patient compliance to trial procedures
- age ≥ 18 years
- Written informed consent
- Adequate BM function (ANC ≥ 1.5x109/L, Platelets ≥ 100x109/L, HgB > 9g/dl)
- Adequate liver function (bilirubin <G2, transaminases no more than 3xULN/<5xULN in present of liver metastases).
- Normal level of alkaline phosphatase and creatinine.
- If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for ninety(90) days after end of treatment.
Who cannot join
- No tumor tissue available or patient negative for ROS1 translocation or MET amplification
- Absence of any measurable lesion
- For ROS1+ patients: Previous therapy with crizotinib or any anti-ALK agent
- For MET amplified patients: Evidence of MET amplification in tumor tissue collected in EGFR mutant patient at time of EGFR-TKI acquired resistance occurrence. An EGFR mutant patient is eligible if MET amplification is detected in a tumor specimen collected before starting an EGFR-TKI
- No previous chemotherapy
- Concomitant radiotherapy or chemotherapy.
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- Previous radiotherapy on the target lesion(s). If all sites were included in radiotherapy fields patient is eligible only if there is evidence of progressive disease after completion of radiotherapy.
- Symptomatic brain metastases
- Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin
- Pregnancy or lactating
- Other serious illness or medical condition potentially interfering with the study
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
Italy26 sites, 23 recruiting
- Recruiting
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
Arezzo, 52100
Sergio Bracarda, +39 0575255438, sergio.bracarda@usl8.toscana.it
- Recruiting
Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica
Avellino, 83100
Cesare Gridelli, 0825203945, cgridelli@libero.it
- Recruiting
IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica
Bari, 70124
Domenico Galetta, +39 0805555418, galetta@teseo.it
- Active, not recruiting
Ospedale Versilia- Oncologia
Camaiore, Lucca, 55041
- Recruiting
Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica
Faenza, Ravenna, 48018
Stefano Tamberi, +39 0546601274, s.tamberi@ausl.ra.it
- Recruiting
A.O.U. Careggi- S.C. Oncologia Medica 1
Florence, 50134
Francesco Di Costanzo, +39 0557947298, adicostanzo.oncmed@hotmail.com
- Recruiting
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
Genova, 16132
Francesco Grossi, +39 0105600385, fg1965@libero.it
- Not yet recruiting
Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
Livorno, 57124
Federico Cappuzzo, +39 0586223189, f.cappuzzo@gmail.com
- Active, not recruiting
Ospedale Campo di Marte- U.O.C. di Oncologia Medica
Lucca, 55100
- Recruiting
Ospedale Umberto I°- Unità Operativa di Oncologia
Lugo, Ravenna, 48022
Claudio Dazzi, +39 0545214088, c.dazzi@ausl.ra.it
- Recruiting
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
Meldola, Forlì- Cesena, 47014
Angelo Delmonte, +39 0543739100, angelo.delmonte@irst.emr.it
- Recruiting
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
Milan, 20141
Filippo De Marinis, MD, +39 0257489482, Filippo.DeMarinis@ieo.it
- Recruiting
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
Modena, 41124
Fausto Barbieri, +39 0594224385, barbieri.fausto@policlinico.mo.it
- Recruiting
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare
Naples, 80131
Alessandro Morabito, +39 0815903631, alessandro.morabito@usc-intnapoli.net
- Recruiting
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
Negrar, Verona, 37024
Stefania Gori, +39 0456013472, stefania.gori@sacrocuore.it
- Recruiting
A.O.U. "Maggiore della Carità"- Dipartimento Oncologico
Novara, 28100
Gloria Borra, +39 03213733989, gloria.borra@libero.it
- Recruiting
Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
Padova, 35128
Adolfo Favaretto, +39 0498215620, agfavaretto@gmail.com
- Recruiting
Casa di Cura La Maddalena- U.O. Oncologia medica
Palermo, 90146
Vittorio Gebbia, +39 0916806111, vittorio.gebbia@tin.it
- Recruiting
Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
Parma, 43126
Marcello Tiseo, +39 0521702316, mtiseo@ao.pr.it
- Recruiting
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
Perugia, 06132
Lucio Crinò, MD, 0755784099, lucio.crino@ospedale.perugia.it
- Recruiting
Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico
Pisa, 56124
Antonio Chella, +39 050995340, anto.kell@tiscali.it
- Recruiting
Ospedale di Ravenna- Oncologia Medica
Ravenna, 48121
Federico Cappuzzo, +39 0544285247, f.cappuzzo@googlemail.com
- Recruiting
Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia
Rimini, 47900
Maximilian Papi, +39 0541705413, mpapi@auslrn.net
- Recruiting
A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica
Saronno, Varese, 21047
Claudio Verusio, +39 029613576, cverusio@aobusto.it
- Active, not recruiting
Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
Sassari, 07100
- Recruiting
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
Verona, 37134
Emilio Bria, +39 0458128124, emiliobria@yahoo.it
About this study
Official title: Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
Phase II, two arms, parallel, non comparative study with crizotinib in patients with ROS 1 translocation or MET amplification or MET exon 14 mutation
Read the detailed description
This is a phase II, prospective, two arms, parallel, non comparative study with crizotinib in pretreated NSCLC patients with ROS1 translocation or MET amplification or MET exon 14 mutation (figure 1). Patients with locally advanced or metastatic NSCLC, pretreated with at least one previous chemotherapy line and with at least one measurable tumor lesion will be considered eligible for the trial. All potentially eligible patients will be evaluated for MET and ROS1 by FISH to detect MET amplification or ROS1 translocation. MET mutation will be assessed using direct sequencing or high sensitive methods. After evaluation of inclusion and exclusion criteria, and after signature of informed consent form, all MET amplified or MET exon 14 mutation or ROS1 translocated eligible patients will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Crizotinib
- Keywords
- MET amplification, ROS1 translocation, Crizotinib
- 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.
CrizotinibDrug
Also called XALKORI
Eligible patients with ROS1 translocation or MET amplification will be treated with Crizotinib at the standard dose of 250 mg BID. The dose of crizotinib may be adjusted depending on the type and severity of toxicity encountered
| Study group | Role | What they receive |
|---|---|---|
| Patients with MET amplification or MET exon 14 mutation | Experimental | Pretreated NSCLC patients with MET amplification or MET exon 14 mutation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal. Receives: Drug: Crizotinib |
| Patients with ROS1 translocation | Experimental | Pretreated NSCLC patients with ROS1 translocation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal. Receives: Drug: Crizotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Secondary outcomes (5)
Progression-free survival (PFS)
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Overall Survival (OS)
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Correlation with additional tumor biomarkers in tumor tissue or blood
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) or MET exon 14 mutation
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startDec 2014
- Primary completionJun 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Ricerca Traslazionale
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lucio Crinò, Principal investigator, Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499614
- Sponsor's protocol ID
- FoRT 01/2014
- Acronym
- METROS
- Status last verified
- Oct 2017
- First submitted
- 30 Mar 2015
- Last updated
- 25 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chiari R, Ricciuti B, Landi L, Morelli AM, Delmonte A, Spitaleri G, Cortinovis DL, Lamberti G, Facchinetti F, Pilotto S, Verusio C, Chella A, Bonanno L, Galetta D, Cappuzzo F. ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS). Clin Lung Cancer. 2020 Jan;21(1):15-20. doi: 10.1016/j.cllc.2019.06.012. Epub 2019 Jun 18.
PubMed 31607443
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
- ClinicalTrials.gov ID
- NCT02499614
- Acronym / sponsor ID
- METROS / FoRT 01/2014
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- MET amplification, ROS1 translocation, Crizotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Fondazione Ricerca TraslazionaleUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II, two arms, parallel, non comparative study with crizotinib in patients with ROS 1 translocation or MET amplification or MET exon 14 mutation
Detailed description
This is a phase II, prospective, two arms, parallel, non comparative study with crizotinib in pretreated NSCLC patients with ROS1 translocation or MET amplification or MET exon 14 mutation (figure 1). Patients with locally advanced or metastatic NSCLC, pretreated with at least one previous chemotherapy line and with at least one measurable tumor lesion will be considered eligible for the trial. All potentially eligible patients will be evaluated for MET and ROS1 by FISH to detect MET amplification or ROS1 translocation. MET mutation will be assessed using direct sequencing or high sensitive methods. After evaluation of inclusion and exclusion criteria, and after signature of informed consent form, all MET amplified or MET exon 14 mutation or ROS1 translocated eligible patients will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with MET amplification or MET exon 14 mutation | Experimental | Drug: CrizotinibPretreated NSCLC patients with MET amplification or MET exon 14 mutation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal. |
| Patients with ROS1 translocation | Experimental | Drug: CrizotinibPretreated NSCLC patients with ROS1 translocation with locally advanced or metastatic NSCLC and with at least one measurable tumor lesion will be considered eligible for the trial and they will receive crizotinib 250 mg BID p.o until disease progression, unacceptable toxicity or patient refusal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed diagnosis of NSCLC
- Availability of tumor tissue for ROS1 and MET analyses
- Patient positive for ROS1 translocation or MET amplification
- At least one radiological measurable disease according to RECIST criteria (Response Evaluation Criteria in Solid Tumors )
- At least 1 previous standard chemotherapy regimen
Key exclusion criteria (11 listed)
- No tumor tissue available or patient negative for ROS1 translocation or MET amplification
- Absence of any measurable lesion
- For ROS1+ patients: Previous therapy with crizotinib or any anti-ALK agent
- For MET amplified patients: Evidence of MET amplification in tumor tissue collected in EGFR mutant patient at time of EGFR-TKI acquired resistance occurrence. An EGFR mutant patient is eligible if MET amplification is detected in a tumor specimen collected before starting an EGFR-TKI
- No previous chemotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CrizotinibAlso: XALKORIEligible patients with ROS1 translocation or MET amplification will be treated with Crizotinib at the standard dose of 250 mg BID. The dose of crizotinib may be adjusted depending on the type and severity of toxicity encountered | Drug | Patients with MET amplification or MET exon 14 mutation, Patients with ROS1 translocation |
Primary outcome
Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
5 secondary outcomes
Progression-free survival (PFS)
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Overall Survival (OS)
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Correlation with additional tumor biomarkers in tumor tissue or blood
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) or MET exon 14 mutation
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- Derived from this study: PubMed 31607443Chiari R, Ricciuti B, Landi L, Morelli AM, Delmonte A, Spitaleri G, Cortinovis DL, Lamberti G, Facchinetti F, Pilotto S, Verusio C, Chella A, Bonanno L, Galetta D, Cappuzzo F. ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS). Clin Lung Cancer. 2020 Jan;21(1):15-20. doi: 10.1016/j.cllc.2019.06.012. Epub 2019 Jun 18.
- Fondazione FoRTLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lucio Crinò principal investigator
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
26 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crizotinib in people with Carcinoma, Non-Small-Cell Lung, run by Fondazione Ricerca Traslazionale at 26 sites in Italy.
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 11 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: status not confirmed, as of the sponsor's last update on 25 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Federico Cappuzzo (+39 010 8398491 / 92, f.cappuzzo@fondazionefort.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation (time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 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 NCT02499614, 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 25 Oct 2017.