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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— 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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02499614
• Other study ID #: FoRT 01/2014
• Status: Recruiting
• Phase: Phase 2
• First received: March 30, 2015
• Last updated: October 23, 2017
• Start date: December 2014
• Est. completion date: December 2018

Study information

• Verified date: October 2017
• Source: Fondazione Ricerca Traslazionale
• Contact: Federico Cappuzzo
• Phone: +39 010 8398491 / 92
• Email: f.cappuzzo[@]fondazionefort.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• 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

Locations

Country	Name	City	State
Italy	Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8	Arezzo
Italy	Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"- U.O. di Oncologia Medica	Avellino
Italy	IRCCS Istituto Tumori "Giovanni Paolo II"- U.O. Oncologia Medica	Bari
Italy	Ospedale Versilia- Oncologia	Camaiore	Lucca
Italy	Ospedale per gli Infermi - Presidio Ospedaliero di Faenza- Unità Operativa di Oncologia Medica	Faenza	Ravenna
Italy	A.O.U. Careggi- S.C. Oncologia Medica 1	Firenze
Italy	IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari	Genova
Italy	Ospedale Civile Livorno- U.O. Dipartimento di Oncologia Medica	Livorno
Italy	Ospedale Campo di Marte- U.O.C. di Oncologia Medica	Lucca
Italy	Ospedale Umberto I°- Unità Operativa di Oncologia	Lugo	Ravenna
Italy	IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica	Meldola	Forlì- Cesena
Italy	Istituto Europeo di Oncologia - Divisione di Oncologia Toracica	Milano
Italy	A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio	Modena
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- Oncologia Medica Dipartimento Toraco-Polmonare	Napoli
Italy	Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica	Negrar	Verona
Italy	A.O.U. "Maggiore della Carità"- Dipartimento Oncologico	Novara
Italy	Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2	Padova
Italy	Casa di Cura La Maddalena- U.O. Oncologia medica	Palermo
Italy	Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica	Parma
Italy	Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia	Perugia
Italy	Azienda Ospedaliero Universitaria Pisana (AOUP)- Pneumo-Oncologia - Dipartimento Cardio-Toracico	Pisa
Italy	Ospedale di Ravenna- Oncologia Medica	Ravenna
Italy	Ospedale "Infermi" Rimini- UU.OO. Oncologia ed Ematologia	Rimini
Italy	A. O. "Ospedale di Circolo" di Busto Arsizio- Struttura Complessa di Oncologia Medica	Saronno	Varese
Italy	Osp. Civile SS. Annunziata- U.O.C di Oncologia Medica	Sassari
Italy	Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Ricerca Traslazionale

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate to crizotinib in patients with ROS1 translocation or MET amplification or MET exon 14 mutation		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	Progression-free survival (PFS)		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	Overall Survival (OS)		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	Toxicity analysis: Incidence of Grade 3-4 Grade Toxicity graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0		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	Correlation with additional tumor biomarkers in tumor tissue or blood		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	Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio = 5) or MET exon 14 mutation		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

External Links

•   Fondazione FoRT