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

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

Tracking Information

• First Submitted Date: March 30, 2015
• First Posted Date: July 16, 2015
• Last Update Posted Date: October 25, 2017
• Study Start Date: December 2014
• Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: 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)
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

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

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 23, 2017): 80
• Original Estimated Enrollment (submitted: July 14, 2015): 40
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT02499614
• Other Study ID Numbers: FoRT 01/2014
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fondazione Ricerca Traslazionale
• Original Responsible Party: Same as current
• Current Study Sponsor: Fondazione Ricerca Traslazionale
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Fondazione Ricerca Traslazionale
• Verification Date: October 2017