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

October 23, 2017 updated by: Fondazione Ricerca Traslazionale

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Arezzo, Italy, 52100
        • Recruiting
        • Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
        • Contact:
      • Avellino, Italy, 83100
        • Recruiting
        • Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica
        • Contact:
      • Bari, Italy, 70124
        • Recruiting
        • IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica
        • Contact:
      • Firenze, Italy, 50134
        • Recruiting
        • A.O.U. Careggi- S.C. Oncologia Medica 1
        • Contact:
      • Genova, Italy, 16132
        • Recruiting
        • IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
        • Contact:
      • Livorno, Italy, 57124
        • Not yet recruiting
        • Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica
        • Contact:
      • Lucca, Italy, 55100
        • Active, not recruiting
        • Ospedale Campo di Marte- U.O.C. di Oncologia Medica
      • Milano, Italy, 20141
        • Recruiting
        • Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
        • Contact:
      • Modena, Italy, 41124
        • Recruiting
        • A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
        • Contact:
      • Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare
        • Contact:
      • Novara, Italy, 28100
        • Recruiting
        • A.O.U. "Maggiore della Carità"- Dipartimento Oncologico
        • Contact:
      • Padova, Italy, 35128
        • Recruiting
        • Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
        • Contact:
      • Palermo, Italy, 90146
        • Recruiting
        • Casa di Cura La Maddalena- U.O. Oncologia medica
        • Contact:
      • Parma, Italy, 43126
        • Recruiting
        • Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
        • Contact:
      • Perugia, Italy, 06132
        • Recruiting
        • Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
        • Contact:
      • Pisa, Italy, 56124
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico
        • Contact:
      • Ravenna, Italy, 48121
        • Recruiting
        • Ospedale di Ravenna- Oncologia Medica
        • Contact:
      • Rimini, Italy, 47900
        • Recruiting
        • Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia
        • Contact:
      • Sassari, Italy, 07100
        • Active, not recruiting
        • Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica
      • Verona, Italy, 37134
        • Recruiting
        • Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
        • Contact:
    • Forlì- Cesena
      • Meldola, Forlì- Cesena, Italy, 47014
        • Recruiting
        • IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
        • Contact:
    • Lucca
      • Camaiore, Lucca, Italy, 55041
        • Active, not recruiting
        • Ospedale Versilia- Oncologia
    • Ravenna
      • Faenza, Ravenna, Italy, 48018
        • Recruiting
        • Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica
        • Contact:
      • Lugo, Ravenna, Italy, 48022
        • Recruiting
        • Ospedale Umberto I°- Unità Operativa di Oncologia
        • Contact:
    • Varese
      • Saronno, Varese, Italy, 21047
        • Recruiting
        • A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica
        • Contact:
    • Verona
      • Negrar, Verona, Italy, 37024
        • Recruiting
        • Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • XALKORI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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

Outcome Measure
Time Frame
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
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
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Ricerca Traslazionale

Investigators

  • Principal Investigator: Lucio Crinò, Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Anticipated)

June 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

March 30, 2015

First Submitted That Met QC Criteria

July 14, 2015

First Posted (Estimate)

July 16, 2015

Study Record Updates

Last Update Posted (Actual)

October 25, 2017

Last Update Submitted That Met QC Criteria

October 23, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FoRT 01/2014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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