Crizotinib in ALK Rearranged Non-small-cell Lung Cancer

• Conditions: Advanced Cancer; Metastatic Cancer; Non Small Cell Lung Cancer

• Registration Number: NCT04317651
• Lead Sponsor: Fondazione Ricerca Traslazionale

Brief Summary

This is a multicenter, observational, retrospective cohort study aimed at assessing the efficacy and safety of crizotinib in ALK positive NSCLC treated in real life setting.

Detailed Description

Primary efficacy objective:

To assess the efficacy of crizotinib in real life setting

Secondary objectives:

1. To evaluate the therapeutic response to crizotinib-based treatment

2. To identify additional biomarkers selectively present in the ALK positive population

3. To assess the safety of crizotinib (250 mg/bid) in the treatment of NSCLC in real life setting

Non-small-cell Lung Cancer (NSCLC) remains the leading cause of cancer death in Western Countries. Identification of anaplastic lymphoma kinase (ALK) gene rearrangements reinforced the role of targeted therapies in lung cancer. The EML4-ALK fusion gene is detected in 3-7% of patients with adenocarcinomas of the lung and is associated with specific clinical pathological features, including young age, absent or minimal smoking history and adenocarcinoma histology. However, such clinical features do not properly select patients for ALK inhibitors (ALK-Is) and, consequently, molecular testing is mandatory. Indeed, current guidelines recommend to test ALK rearrangements at diagnosis all patients with advanced lung adenocarcinoma, due to immediate therapeutic implications.

Study Timeline

• Study Start: 2019-05-16
• Status Verified: 2020-03
• Study First Submitted: 2020-03-19
• Study First Submitted QC: 2020-03-20
• Study First Posted: 2020-03-23
• Last Update Submitted: 2020-03-24
• Last Update Posted: 2020-03-25
• Primary Completion: 2021-12
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• 1. Males and Females aged 18 years with diagnosis of advanced or metastatic NSCLC
• 2. Former participation in the Italian NPU program between December 2010 - April 2013 or receiving crizotinib according to 648 legislative Decrete from April 2013 to February 2015 and thereafter in clinical practice up to December 31st, 2017.
• 3. Ascertained compliance to the Crizotinib therapy as prescribed by the relevant physician
• 4. ALK rearrangement report including details of method and cutoff used for ALK testing
• 5. Data on prior therapies
• 6. Data on toxicity
• 7. Data on crizotinib therapy efficacy including response to the therapy and survival
• 8. Data on site of metastases
• 9. Availability of archival tissue (not mandatory)
• 10. Signed Informed Consent for alive and contactable patients

Exclusion Criteria

• 1. Lack of clinical data
• 2. No evidence of ALK rearrangemement
• 3. Early death defined as fatal outcome within 30 days since the first crizotinib dose
• 4. Absence of any radiological assessment
• 5. No data on crizotinib efficacy including survival

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Sistematic review of medical records	Six months	To assess the overall efficacy of crizotinib (250 mg/bid) in terms of Response rate, Progression-Free Survival and Overall Survival in the treatment of NSCLC in real life setting. Median PFS, as reported by a recent metanalysis, is 9.4 months (first and second line together) corresponding to a 12 months PFS rate of about 40%. The analysis of 500 patients will allow to estimate the median PFS with a semi-width 95% confidence interval of 1.2 months. OS will be calculated from the first day of treatment until the date of death from any cause. Any patient not known to have died at the time of data analysis will be censored at the time of the last recorded date on which the patient was known to be alive. Time to events will be summarized using Kaplan-Meier estimation.; ORR, defined as the proportion of patients with a best overall response of either Complete response or Partial response, will be calculated based on disease status evaluated by the investigator according to RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
Secondary Objectives	Six months	1. To define clinical and biological characteristics of patients not responding to crizotinib therapy at the first tumor assessment versus individuals with complete or deep partial response (\> 50% reduction in the sum of target lesions); 2. To define additional biomarkers selectively present in the ALK positive population; 3. To explore outcome of individuals with brain metastases; 4. To define timing of local ablative therapy in presence of brain metastas

Trial Locations

Locations (23)

Ospedale Oncologico Regionale - Centro di Riferimento Oncologico di Basilicata; 🇮🇹 Rionero In Vulture, Potenza, Italy

IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); 🇮🇹 Meldola, Ravenna, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale; 🇮🇹 Napoli, Italy

A.O.R.N dei Colli - Ospedale Monaldi; 🇮🇹 Napoli, Italy

A.O. San Gerardo; 🇮🇹 Monza, Milano, Italy

Sacro Cuore- Don Calabria Hospital; 🇮🇹 Negrar, Verona, Italy

Ospedale Santa Maria della Misericordia - Azienda Ospedaliera di Perugia; 🇮🇹 Perugia, Italy

Ospedale Versilia; 🇮🇹 Camaiore, Lucca, Italy

IRCCS Istituto Tumori Giovanni Paolo II; 🇮🇹 Bari, Italy

Ospedale Giovanni Paolo II ASL-2 Olbia; 🇮🇹 Olbia, Italy

Istituto Oncologico Veneto IRCCS; 🇮🇹 Padova, Italy

Azienda Ospedaliero-Universitaria Careggi; 🇮🇹 Firenze, Italy

A.O.U. San Luigi Gonzaga; 🇮🇹 Orbassano, Torino, Italy

Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"; 🇮🇹 Avellino, Italy

AO Papardo; 🇮🇹 Messina, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Azienda Ospedaliera-Universitaria di Parma; 🇮🇹 Parma, Italy

Ospedale di Ravenna; 🇮🇹 Ravenna, Italy

IRCCS- Arcispedale Santa Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Policlinico Universitario "Campus Biomedico" di Roma; 🇮🇹 Roma, Italy

Azienda Ospedaliera San Camillo-Forlanini; 🇮🇹 Roma, Italy

ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi"; 🇮🇹 Varese, Italy

Policlinico 'G.B.Rossi' Borgo Roma - Azienda Ospedaliera Universitaria Integrata (Giampaolo Tortora); 🇮🇹 Verona, Italy