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Recruiting 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

Phase II Interventional Non Small Cell Lung Cancer Metastatic ALK Gene Mutation

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Lorlatinib.
Who it may be relevant to
Registry conditions: Non Small Cell Lung Cancer Metastatic, ALK Gene Mutation. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Italy
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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.

Overview

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.

Interventions

  • 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.

Primary outcome measures

  • 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. [Time frame: Up to 60 months]
Secondary outcome measures (3)
  • Intracranial Progression Free Survival (PFS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib. [Time frame: Up to 60 months]
  • Overall survival (OS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib progression [Time frame: Up to 60 months]
  • Describe the safety of PT/pem-based chemotherapy plus Lorlatinib combination [Time frame: Up to 60 months]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

Italy · 9 centers
  • Centro di Riferimento Oncologico (CRO) IRCCS — Aviano
  • Azienda Ospedaliero-Universitaria Careggi Oncologia Medica — Florence
  • Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia — Lido di Camaiore
  • Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori" — Meldola
  • Fondazione IRCCS San Gerardo dei Tintori — Monza
  • IOV Istituto Oncologico Veneto IRCCS — Padova
  • Azienda Ospedaliero-Universitaria di Parma — Parma
  • Azienda Ospedaliera di Perugia — Perugia
  • … and 1 more center

Identifiers

NCT: NCT06378892 · CRO-2023-78

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗