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
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
| Drug | Synonyms | Arms |
|---|
| Crizotinib | XALKORI | Patients 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
| Name | Type | Description | Interventions |
|---|
| Patients with MET amplification or MET exon 14 mutation | Experimental | 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. | |
| Patients with ROS1 translocation | Experimental | 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. | |
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: | Unknown status |
| Lead Sponsor: | Fondazione Ricerca Traslazionale |
Trial Keywords
- MET amplification
- ROS1 translocation
- Crizotinib
Last Updated
October 25, 2017
