A Study to Evaluate the Combination of Platinum-pemetrexed Based Chemotherapy Plus Lorlatinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) With Exclusively Extracranial Disease Progression on Lorlatinib (ALK-PPL)

A Multicenter Single-arm Phase II Interventional Study to Evaluate the Activity and Safety of the Combination of Platinum-pemetrexed Based Chemotherapy Plus Lorlatinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) With Exclusively Extracranial Disease Progression on Lorlatinib.

This study aims to evaluate the activity and safety of the combination of platinum-pemetrexed based chemotherapy plus Lorlatinib in ALK positive Non-Small Cell Lung Cancer (NSCLC) with exclusively extracranial disease progression on Lorlatinib. Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer Metastatic; ALK Gene Mutation
• Intervention / Treatment: Drug: Lorlatinib

Detailed Description

This is a multicentre, phase II, interventional, prospective, single arm, non-randomised study focused on ALK+ NSCLC with extracranial progression on Lorlatinib.Treatment phase include the period starting from cycle 1 day 1 visit to discontinuation of study therapy and consists of two phases: induction phase and maintenance phase. Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alessandra Bearz; Phone Number: 0434-659294; Email: abearz@cro.it

Study Locations

• Italy
  • Aviano, Italy, 33081
    • Recruiting
    • Centro di Riferimento Oncologico (CRO) IRCCS
    • Contact: Alessandra Bearz; Phone Number: 0434659294; Email: abearz@cro.it
  • Firenze, Italy, 50134
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria Careggi Oncologia Medica
    • Contact: Lorenzo Antonuzzo; Phone Number: 0557947298; Email: antonuzzol@aou-careggi.toscana.it
  • Lido Di Camaiore, Italy, 55049
    • Not yet recruiting
    • Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia
    • Contact: Camerini Andrea; Phone Number: 05846057282; Email: andrea.camerini@uslnordovest.toscana.it
  • Meldola, Italy, 47014
    • Not yet recruiting
    • Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori"
    • Contact: Delmonte Angelo; Phone Number: 0543739100; Email: angelo.delmonte@irst.emr.it
  • Monza, Italy, 20900
    • Not yet recruiting
    • Fondazione IRCCS San Gerardo dei Tintori
    • Contact: Cortinovis Diego Luigi; Phone Number: 0392336040; Email: diegoluigi.cortinovis@irccs-sangerardo.it
  • Padova, Italy, 35128
    • Not yet recruiting
    • IOV Istituto Oncologico Veneto IRCCS
    • Contact: Pasello Giulia; Phone Number: 0498215608; Email: giulia.pasello@iov.veneto.it
  • Parma, Italy, 43126
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria di Parma
    • Contact: Tiseo Marcello; Phone Number: 0521702316; Email: mtiseo@ao.pr.it
  • Perugia, Italy, 06129
    • Not yet recruiting
    • Azienda Ospedaliera di Perugia
    • Contact: Metro Giulio; Phone Number: 0755783695; Email: giulio.metro@ospedale.perugia.it
  • Udine, Italy, 33010
    • Not yet recruiting
    • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
    • Contact: Giacomo Pellizzari; Phone Number: 0432552754; Email: giacomo.pelizzari@asufc.sanita.fvg.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of stage IV ALK positive NSCLC.
• Patients must be in progression extracranially on Lorlatinib; Lorlatinib may be in first- or further-line, without limitations regarding previously received therapies.
• Age at the time of signing the informed consent at least 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have measurable disease according to RECIST 1.1 by computed tomography (CT) and magnetic resonance imaging (MRI).
• Radiologically confirmed multiple extracranial progression on Lorlatinib without progression in the central nervous system (CNS) defined as absence of CNS metastasis or CNS metastasis stable on Lorlatinib and/or stereotactic brain irradiation (SBRT).
• Adequate organ function (kidney, bone marrow and liver).
• Estimated life expectancy of at least 3 months irrespective of the diagnosis of ALK+ NSCLC.
• For women of childbearing potential and males with partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drugs.

Key Exclusion Criteria:

• Known hypersensitivity reaction to one of the compounds or substances used in this protocol.
• Diagnosis of any secondary malignancy within the last 3 years except for: adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, definitively treated nonmetastatic prostate cancer or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Patients deemed unsuitable by the investigator for treatment of chemo-Lorlatinib combination.
• Presence of toxicities contraindicating the continuation of therapy with Lorlatinib.
• Concomitant use of potent CYP3A4/5 inducers.

Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lorlatinib; Lorlatinib 100mg once daily. Carboplatin AUC 5 or Cisplatin 75 mg/m^2 for an induction phase of four cycles. Pemetrexed 500 mg/m^2 during the maintenance phase.

Drug: Lorlatinib; Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. The choice between Carboplatin or Cisplatin is entrusted to the clinician. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Progression Free Survival between patients treated with Pemetrexed (PT)/pem-based chemotherapy plus Lorlatinib after Lorlatinib versus retrospective data of 3,2 months for patients treated with PT/pem-based chemotherapy after Lorlatinib.	PFS defined as the time from study enrollment to the first documented disease progression or death due to any cause, whichever occurs first.	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Progression Free Survival (PFS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib.	Intracranial PFS defined as time from study enrollment until CNS disease progression or death from any cause.	Up to 60 months
Overall survival (OS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib progression	OS is defined as the time from study enrollment until death from any cause.	Up to 60 months
Describe the safety of PT/pem-based chemotherapy plus Lorlatinib combination	Frequency and severity of adverse events graded according to the CTCAE version 5.0.	Up to 60 months

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Disease Progression; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CRO-2023-78

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No