Clinical trial NCT02499614: Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
Official title: Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: MET amplification
ROS1 translocation
Crizotinib
Lead sponsor: Fondazione Ricerca Traslazionale
Sponsor class: OTHER
First posted: 2015-07-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation
timeFrame: 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:
measure: Progression-free survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
measure: Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
timeFrame: 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
measure: Correlation with additional tumor biomarkers in tumor tissue or blood
timeFrame: 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
measure: Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) or MET exon 14 mutation
timeFrame: 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
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
state: Forlì- Cesena
city: Camaiore
country: Italy
facility: Ospedale Versilia- Oncologia
state: Lucca
city: Faenza
country: Italy
facility: Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica
state: Ravenna
city: Lugo
country: Italy
facility: Ospedale Umberto I°- Unità Operativa di Oncologia
state: Ravenna
city: Saronno
country: Italy
facility: A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica
state: Varese
city: Negrar
country: Italy
facility: Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
state: Verona
city: Arezzo
country: Italy
facility: Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
city: Avellino
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica
city: Bari
country: Italy
facility: IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica
city: Firenze
country: Italy
facility: A.O.U. Careggi- S.C. Oncologia Medica 1
city: Genova
country: Italy
facility: IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
city: Livorno
country: Italy
facility: Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
city: Lucca
country: Italy
facility: Ospedale Campo di Marte- U.O.C. di Oncologia Medica
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare
city: Novara
country: Italy
facility: A.O.U. "Maggiore della Carità"- Dipartimento Oncologico
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena- U.O. Oncologia medica
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico
city: Ravenna
country: Italy
facility: Ospedale di Ravenna- Oncologia Medica
city: Rimini
country: Italy
facility: Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia
city: Sassari
country: Italy
facility: Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
city: Verona
country: Italy
facility: Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
Study officials:
affiliation: Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
name: Lucio Crinò
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.