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Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS) (METROS)

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ClinicalTrials.gov Identifier: NCT02499614
Recruitment Status : Recruiting
First Posted : July 16, 2015
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Fondazione Ricerca Traslazionale

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

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Crizotinib Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
Study Start Date : December 2014
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Crizotinib

Arm Intervention/treatment
Experimental: Patients with MET amplification or MET exon 14 mutation
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.
Drug: Crizotinib
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
Other Name: XALKORI

Experimental: Patients with ROS1 translocation
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.
Drug: Crizotinib
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
Other Name: XALKORI




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02499614


Contacts
Contact: Federico Cappuzzo +39 010 8398491 / 92 f.cappuzzo@fondazionefort.org

Locations
Italy
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica Recruiting
Meldola, Forlì- Cesena, Italy, 47014
Contact: Angelo Delmonte    +39 0543739100    angelo.delmonte@irst.emr.it   
Ospedale Versilia- Oncologia Active, not recruiting
Camaiore, Lucca, Italy, 55041
Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica Recruiting
Faenza, Ravenna, Italy, 48018
Contact: Stefano Tamberi    +39 0546601274    s.tamberi@ausl.ra.it   
Ospedale Umberto I°- Unità Operativa di Oncologia Recruiting
Lugo, Ravenna, Italy, 48022
Contact: Claudio Dazzi    +39 0545214088    c.dazzi@ausl.ra.it   
A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica Recruiting
Saronno, Varese, Italy, 21047
Contact: Claudio Verusio    +39 029613576    cverusio@aobusto.it   
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica Recruiting
Negrar, Verona, Italy, 37024
Contact: Stefania Gori    +39 0456013472    stefania.gori@sacrocuore.it   
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8 Recruiting
Arezzo, Italy, 52100
Contact: Sergio Bracarda    +39 0575255438    sergio.bracarda@usl8.toscana.it   
Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica Recruiting
Avellino, Italy, 83100
Contact: Cesare Gridelli    0825203945    cgridelli@libero.it   
IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica Recruiting
Bari, Italy, 70124
Contact: Domenico Galetta    +39 0805555418    galetta@teseo.it   
A.O.U. Careggi- S.C. Oncologia Medica 1 Recruiting
Firenze, Italy, 50134
Contact: Francesco Di Costanzo    +39 0557947298    adicostanzo.oncmed@hotmail.com   
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari Recruiting
Genova, Italy, 16132
Contact: Francesco Grossi    +39 0105600385    fg1965@libero.it   
Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica Not yet recruiting
Livorno, Italy, 57124
Contact: Federico Cappuzzo    +39 0586223189    f.cappuzzo@gmail.com   
Ospedale Campo di Marte- U.O.C. di Oncologia Medica Active, not recruiting
Lucca, Italy, 55100
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica Recruiting
Milano, Italy, 20141
Contact: Filippo De Marinis, MD    +39 0257489482    Filippo.DeMarinis@ieo.it   
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio Recruiting
Modena, Italy, 41124
Contact: Fausto Barbieri    +39 0594224385    barbieri.fausto@policlinico.mo.it   
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare Recruiting
Napoli, Italy, 80131
Contact: Alessandro Morabito    +39 0815903631    alessandro.morabito@usc-intnapoli.net   
A.O.U. "Maggiore della Carità"- Dipartimento Oncologico Recruiting
Novara, Italy, 28100
Contact: Gloria Borra    +39 03213733989    gloria.borra@libero.it   
Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2 Recruiting
Padova, Italy, 35128
Contact: Adolfo Favaretto    +39 0498215620    agfavaretto@gmail.com   
Casa di Cura La Maddalena- U.O. Oncologia medica Recruiting
Palermo, Italy, 90146
Contact: Vittorio Gebbia    +39 0916806111    vittorio.gebbia@tin.it   
Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica Recruiting
Parma, Italy, 43126
Contact: Marcello Tiseo    +39 0521702316    mtiseo@ao.pr.it   
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia Recruiting
Perugia, Italy, 06132
Contact: Lucio Crinò, MD    0755784099    lucio.crino@ospedale.perugia.it   
Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico Recruiting
Pisa, Italy, 56124
Contact: Antonio Chella    +39 050995340    anto.kell@tiscali.it   
Ospedale di Ravenna- Oncologia Medica Recruiting
Ravenna, Italy, 48121
Contact: Federico Cappuzzo    +39 0544285247    f.cappuzzo@googlemail.com   
Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia Recruiting
Rimini, Italy, 47900
Contact: Maximilian Papi    +39 0541705413    mpapi@auslrn.net   
Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica Active, not recruiting
Sassari, Italy, 07100
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica Recruiting
Verona, Italy, 37134
Contact: Emilio Bria    +39 0458128124    emiliobria@yahoo.it   
Sponsors and Collaborators
Fondazione Ricerca Traslazionale
Investigators
Principal Investigator: Lucio Crinò Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia

Additional Information:
Responsible Party: Fondazione Ricerca Traslazionale
ClinicalTrials.gov Identifier: NCT02499614     History of Changes
Other Study ID Numbers: FoRT 01/2014
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017

Keywords provided by Fondazione Ricerca Traslazionale:
MET amplification
ROS1 translocation
Crizotinib

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action