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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 : Unknown
Verified October 2017 by Fondazione Ricerca Traslazionale.
Recruitment status was:  Recruiting
First Posted : July 16, 2015
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Fondazione Ricerca Traslazionale

Tracking Information
First Submitted Date  ICMJE March 30, 2015
First Posted Date  ICMJE July 16, 2015
Last Update Posted Date October 25, 2017
Study Start Date  ICMJE December 2014
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
Response rate to crizotinib in patients with ROS1 translocation or MET amplification [ 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5) [ 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or ROS1 Translocation (METROS)
Official Title  ICMJE Crizotinib in Pretreated Metastatic Non-small-cell Lung Cancer With MET Amplification or MET Exon 14 Mutation or ROS1 Translocation (METROS)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Crizotinib
  • 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.
    Intervention: Drug: Crizotinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 23, 2017)
80
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2015)
40
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02499614
Other Study ID Numbers  ICMJE FoRT 01/2014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fondazione Ricerca Traslazionale
Study Sponsor  ICMJE Fondazione Ricerca Traslazionale
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lucio Crinò Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia
PRS Account Fondazione Ricerca Traslazionale
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP