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

NCT06378892 | Recruiting Phase 2

• 1 other identifier: CRO-2023-78
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 9

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.

Conditions

Non Small Cell Lung Cancer Metastatic; ALK Gene Mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Intracranial Progression Free Survival (PFS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib.

  Up to 60 months

• Overall survival (OS) in patients treated with PT/pem-based chemotherapy plus Lorlatinib after Lorlatinib progression

  Up to 60 months

• Describe the safety of PT/pem-based chemotherapy plus Lorlatinib combination

  Up to 60 months

Study Arms (1)

Lorlatinib

EXPERIMENTAL

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

Interventions

Lorlatinib DRUG

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.

Lorlatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro di Riferimento Oncologico - Aviano: lead

Study Sites (9)

Centro di Riferimento Oncologico (CRO) IRCCS

Aviano, 33081, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Careggi Oncologia Medica

Florence, 50134, Italy

NOT YET RECRUITING

Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia

Lido di Camaiore, 55049, Italy

NOT YET RECRUITING

Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori"

Meldola, 47014, Italy

NOT YET RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

NOT YET RECRUITING

IOV Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

NOT YET RECRUITING

Azienda Ospedaliera di Perugia

Perugia, 06129, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)

Udine, 33010, Italy

NOT YET RECRUITING

MeSH Terms

Interventions

lorlatinib

Central Study Contacts

Alessandra Bearz

CONTACT

0434-659294; abearz@cro.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 23, 2024
• Study Start: March 15, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 23, 2024

Record last verified: 2024-04

Locations

IT (9)