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

Non Small Cell Lung Cancer Metastatic Clinical Trial

— ALK-PPL  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06378892
• Other study ID #: CRO-2023-78
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2024
• Est. completion date: May 2028

Study information

• Verified date: April 2024
• Source: Centro di Riferimento Oncologico - Aviano
• Contact: Alessandra Bearz
• Phone: 0434-659294
• Email: abearz[@]cro.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ALK Gene Mutation
• Carcinoma, Non-Small-Cell Lung
• Disease Progression
• Lung Neoplasms
• Non Small Cell Lung Cancer Metastatic

Intervention

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.

Locations

Country	Name	City	State
Italy	Centro di Riferimento Oncologico (CRO) IRCCS	Aviano
Italy	Azienda Ospedaliero-Universitaria Careggi Oncologia Medica	Firenze
Italy	Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia	Lido Di Camaiore
Italy	Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori"	Meldola
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza
Italy	IOV Istituto Oncologico Veneto IRCCS	Padova
Italy	Azienda Ospedaliero-Universitaria di Parma	Parma
Italy	Azienda Ospedaliera di Perugia	Perugia
Italy	Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)	Udine

Sponsors (1)

Lead Sponsor	Collaborator
Centro di Riferimento Oncologico - Aviano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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