Clinical trial NCT06378892: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer Metastatic
ALK Gene Mutation
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2024-04-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Up to 60 months
Secondary outcomes:
measure: Intracranial Progression Free Survival (PFS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib.
timeFrame: Up to 60 months
measure: Overall survival (OS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib progression
timeFrame: Up to 60 months
measure: Describe the safety of PT/pem-based chemotherapy plus Lorlatinib combination
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO) IRCCS
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi Oncologia Medica
city: Lido Di Camaiore
country: Italy
facility: Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori"
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Padova
country: Italy
facility: IOV Istituto Oncologico Veneto IRCCS
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
Study officials:
References: