Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
METROS
1 other identifier
interventional
80
1 country
26
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2014
Typical duration for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2014
CompletedFirst Submitted
Initial submission to the registry
March 30, 2015
CompletedFirst Posted
Study publicly available on registry
July 16, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2018
CompletedOctober 25, 2017
October 1, 2017
3.5 years
March 30, 2015
October 23, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
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)
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)
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
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
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
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
Study Arms (2)
Patients with MET amplification or MET exon 14 mutation
EXPERIMENTALPretreated 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
EXPERIMENTALPretreated 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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)
- 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.
You may not qualify if:
- 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.
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
Meldola, Forlì- Cesena, 47014, Italy
Ospedale Versilia- Oncologia
Camaiore, Lucca, 55041, Italy
Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica
Faenza, Ravenna, 48018, Italy
Ospedale Umberto I°- Unità Operativa di Oncologia
Lugo, Ravenna, 48022, Italy
A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica
Saronno, Varese, 21047, Italy
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
Negrar, Verona, 37024, Italy
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
Arezzo, 52100, Italy
Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica
Avellino, 83100, Italy
IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica
Bari, 70124, Italy
A.O.U. Careggi- S.C. Oncologia Medica 1
Florence, 50134, Italy
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
Genova, 16132, Italy
Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
Livorno, 57124, Italy
Ospedale Campo di Marte- U.O.C. di Oncologia Medica
Lucca, 55100, Italy
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
Milan, 20141, Italy
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
Modena, 41124, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare
Napoli, 80131, Italy
A.O.U. "Maggiore della Carità"- Dipartimento Oncologico
Novara, 28100, Italy
Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
Padua, 35128, Italy
Casa di Cura La Maddalena- U.O. Oncologia medica
Palermo, 90146, Italy
Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
Parma, 43126, Italy
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
Perugia, 06132, Italy
Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico
Pisa, 56124, Italy
Ospedale di Ravenna- Oncologia Medica
Ravenna, 48121, Italy
Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia
Rimini, 47900, Italy
Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
Sassari, 07100, Italy
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
Verona, 37134, Italy
Related Publications (1)
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.
PMID: 31607443DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lucio Crinò
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 30, 2015
First Posted
July 16, 2015
Study Start
December 1, 2014
Primary Completion
June 1, 2018
Study Completion
December 1, 2018
Last Updated
October 25, 2017
Record last verified: 2017-10