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

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Crizotinib
Sponsored by
Fondazione Ricerca Traslazionale
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring MET amplification, ROS1 translocation, Crizotinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia MedicaRecruiting
  • Ospedale Versilia- Oncologia
  • Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia MedicaRecruiting
  • Ospedale Umberto I°- Unità Operativa di OncologiaRecruiting
  • A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia MedicaRecruiting
  • Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia MedicaRecruiting
  • Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8Recruiting
  • Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia MedicaRecruiting
  • IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia MedicaRecruiting
  • A.O.U. Careggi- S.C. Oncologia Medica 1Recruiting
  • IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori PolmonariRecruiting
  • Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
  • Ospedale Campo di Marte- U.O.C. di Oncologia Medica
  • Istituto Europeo di Oncologia - Divisione di Oncologia ToracicaRecruiting
  • A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato RespiratorioRecruiting
  • Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-PolmonareRecruiting
  • A.O.U. "Maggiore della Carità"- Dipartimento OncologicoRecruiting
  • Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2Recruiting
  • Casa di Cura La Maddalena- U.O. Oncologia medicaRecruiting
  • Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia MedicaRecruiting
  • Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di PerugiaRecruiting
  • Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-ToracicoRecruiting
  • Ospedale di Ravenna- Oncologia MedicaRecruiting
  • Ospedale "Infermi" Rimini- UU.OO. Oncologia ed EmatologiaRecruiting
  • Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
  • Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia MedicaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patients with MET amplification or MET exon 14 mutation

Patients with ROS1 translocation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation

Secondary Outcome Measures

Progression-free survival (PFS)
Overall Survival (OS)
Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
Correlation with additional tumor biomarkers in tumor tissue or blood
Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) or MET exon 14 mutation

Full Information

First Posted
March 30, 2015
Last Updated
October 23, 2017
Sponsor
Fondazione Ricerca Traslazionale
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1. Study Identification

Unique Protocol Identification Number
NCT02499614
Brief Title
Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
Acronym
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Unknown status
Study Start Date
December 2014 (undefined)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Ricerca Traslazionale

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
MET amplification, ROS1 translocation, Crizotinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with MET amplification or MET exon 14 mutation
Arm Type
Experimental
Arm Description
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.
Arm Title
Patients with ROS1 translocation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Crizotinib
Other Intervention Name(s)
XALKORI
Intervention Description
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
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Federico Cappuzzo
Phone
+39 010 8398491 / 92
Email
f.cappuzzo@fondazionefort.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucio Crinò
Organizational Affiliation
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
City
Meldola
State/Province
Forlì- Cesena
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angelo Delmonte
Phone
+39 0543739100
Email
angelo.delmonte@irst.emr.it
Facility Name
Ospedale Versilia- Oncologia
City
Camaiore
State/Province
Lucca
ZIP/Postal Code
55041
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica
City
Faenza
State/Province
Ravenna
ZIP/Postal Code
48018
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefano Tamberi
Phone
+39 0546601274
Email
s.tamberi@ausl.ra.it
Facility Name
Ospedale Umberto I°- Unità Operativa di Oncologia
City
Lugo
State/Province
Ravenna
ZIP/Postal Code
48022
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudio Dazzi
Phone
+39 0545214088
Email
c.dazzi@ausl.ra.it
Facility Name
A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica
City
Saronno
State/Province
Varese
ZIP/Postal Code
21047
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudio Verusio
Phone
+39 029613576
Email
cverusio@aobusto.it
Facility Name
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
City
Negrar
State/Province
Verona
ZIP/Postal Code
37024
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefania Gori
Phone
+39 0456013472
Email
stefania.gori@sacrocuore.it
Facility Name
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
City
Arezzo
ZIP/Postal Code
52100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sergio Bracarda
Phone
+39 0575255438
Email
sergio.bracarda@usl8.toscana.it
Facility Name
Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica
City
Avellino
ZIP/Postal Code
83100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cesare Gridelli
Phone
0825203945
Email
cgridelli@libero.it
Facility Name
IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica
City
Bari
ZIP/Postal Code
70124
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Domenico Galetta
Phone
+39 0805555418
Email
galetta@teseo.it
Facility Name
A.O.U. Careggi- S.C. Oncologia Medica 1
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Di Costanzo
Phone
+39 0557947298
Email
adicostanzo.oncmed@hotmail.com
Facility Name
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
City
Genova
ZIP/Postal Code
16132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Grossi
Phone
+39 0105600385
Email
fg1965@libero.it
Facility Name
Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
City
Livorno
ZIP/Postal Code
57124
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Federico Cappuzzo
Phone
+39 0586223189
Email
f.cappuzzo@gmail.com
Facility Name
Ospedale Campo di Marte- U.O.C. di Oncologia Medica
City
Lucca
ZIP/Postal Code
55100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
City
Milano
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Filippo De Marinis, MD
Phone
+39 0257489482
Email
Filippo.DeMarinis@ieo.it
Facility Name
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
City
Modena
ZIP/Postal Code
41124
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fausto Barbieri
Phone
+39 0594224385
Email
barbieri.fausto@policlinico.mo.it
Facility Name
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alessandro Morabito
Phone
+39 0815903631
Email
alessandro.morabito@usc-intnapoli.net
Facility Name
A.O.U. "Maggiore della Carità"- Dipartimento Oncologico
City
Novara
ZIP/Postal Code
28100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gloria Borra
Phone
+39 03213733989
Email
gloria.borra@libero.it
Facility Name
Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
City
Padova
ZIP/Postal Code
35128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adolfo Favaretto
Phone
+39 0498215620
Email
agfavaretto@gmail.com
Facility Name
Casa di Cura La Maddalena- U.O. Oncologia medica
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vittorio Gebbia
Phone
+39 0916806111
Email
vittorio.gebbia@tin.it
Facility Name
Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
City
Parma
ZIP/Postal Code
43126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcello Tiseo
Phone
+39 0521702316
Email
mtiseo@ao.pr.it
Facility Name
Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
City
Perugia
ZIP/Postal Code
06132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucio Crinò, MD
Phone
0755784099
Email
lucio.crino@ospedale.perugia.it
Facility Name
Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Chella
Phone
+39 050995340
Email
anto.kell@tiscali.it
Facility Name
Ospedale di Ravenna- Oncologia Medica
City
Ravenna
ZIP/Postal Code
48121
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Federico Cappuzzo
Phone
+39 0544285247
Email
f.cappuzzo@googlemail.com
Facility Name
Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia
City
Rimini
ZIP/Postal Code
47900
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maximilian Papi
Phone
+39 0541705413
Email
mpapi@auslrn.net
Facility Name
Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
City
Sassari
ZIP/Postal Code
07100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilio Bria
Phone
+39 0458128124
Email
emiliobria@yahoo.it

12. IPD Sharing Statement

Citations:
PubMed Identifier
31607443
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.
Results Reference
derived
Links:
URL
http://www.fondazionefort.org/
Description
Fondazione FoRT

Learn more about this trial

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

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