Clinical Trials /

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

NCT02499614

Description:

Phase II, two arms, parallel, non comparative study with crizotinib in patients with ROS 1 translocation or MET amplification or MET exon 14 mutation

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: FoRT 01/2014
  • NCT ID: NCT02499614

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
CrizotinibXALKORIPatients with MET amplification or MET exon 14 mutation

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Patients with MET amplification or MET exon 14 mutationExperimentalPretreated 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.
  • Crizotinib
Patients with ROS1 translocationExperimentalPretreated 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.
  • Crizotinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
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
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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fondazione Ricerca Traslazionale

Trial Keywords

  • MET amplification
  • ROS1 translocation
  • Crizotinib

Last Updated

October 23, 2017