Combining chemotherapy with Lorlatinib for ALK positive lung cancer
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 is testing if combining chemotherapy with Lorlatinib can help people with ALK positive lung cancer who have seen their disease get worse while on Lorlatinib.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 45 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Centro di Riferimento Oncologico - Aviano Academic / other |
| Drugs / interventions | Lorlatinib, chemotherapy |
| Locations | 9 sites (Aviano and 8 other locations) |
| Trial ID | NCT06378892 on ClinicalTrials.gov |
What this trial studies
This study evaluates the effectiveness and safety of combining platinum-pemetrexed based chemotherapy with Lorlatinib in patients with ALK positive Non-Small Cell Lung Cancer (NSCLC) who have experienced extracranial disease progression while on Lorlatinib. The treatment consists of an induction phase with four cycles of chemotherapy and Lorlatinib, followed by a maintenance phase for those who show a response or stable disease. The study is multicenter and non-randomized, focusing on a specific patient population with measurable disease. Patients will be monitored for disease progression, toxicity, and overall survival.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with stage IV ALK positive NSCLC and measurable extracranial disease progression on Lorlatinib.
Not a fit: Patients with CNS metastasis or those who have not progressed extracranially on Lorlatinib may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new effective treatment option for patients with ALK positive NSCLC experiencing disease progression.
How similar studies have performed: While this specific combination has not been widely tested, similar approaches in treating ALK positive NSCLC have shown promise in other studies.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Aviano and 8 other locations
- Centro di Riferimento Oncologico (CRO) IRCCS — Aviano, Italy (Recruiting)
- Azienda Ospedaliero-Universitaria Careggi Oncologia Medica — Florence, Italy (Not_yet_recruiting)
- Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia — Lido di Camaiore, Italy (Not_yet_recruiting)
- Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori" — Meldola, Italy (Not_yet_recruiting)
- Fondazione IRCCS San Gerardo dei Tintori — Monza, Italy (Not_yet_recruiting)
- IOV Istituto Oncologico Veneto IRCCS — Padova, Italy (Not_yet_recruiting)
- Azienda Ospedaliero-Universitaria di Parma — Parma, Italy (Not_yet_recruiting)
- Azienda Ospedaliera di Perugia — Perugia, Italy (Not_yet_recruiting)
- Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) — Udine, Italy (Not_yet_recruiting)
Study contacts
- Study coordinator: Alessandra Bearz
- Email: abearz@cro.it
- Phone: 0434-659294
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.