Non Small Cell Lung Cancer MetastaticPhase 2ALK-PPLNCT06378892
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
A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer Metastatic and ALK Gene Mutation, run by Centro di Riferimento Oncologico - Aviano at 9 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer Metastatic, ALK Gene Mutation
- What is being tested?
- Lorlatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 9 sitesItaly
- Study dates
- 15 Mar 2024to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Italy9 sites, 9 recruiting
- Recruiting
Centro di Riferimento Oncologico (CRO) IRCCS
Aviano, 33081
Alessandra Bearz, 0434659294, abearz@cro.it
- Not yet recruiting
Azienda Ospedaliero-Universitaria Careggi Oncologia Medica
Florence, 50134
Lorenzo Antonuzzo, 0557947298, antonuzzol@aou-careggi.toscana.it
- Not yet recruiting
Azienda USL Toscana Nord Ovest Oncologia Medica, Ospedale Versilia
Lido di Camaiore, 55049
Camerini Andrea, 05846057282, andrea.camerini@uslnordovest.toscana.it
- Not yet recruiting
Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino amadori"
Meldola, 47014
Delmonte Angelo, 0543739100, angelo.delmonte@irst.emr.it
- Not yet recruiting
Fondazione IRCCS San Gerardo dei Tintori
Monza, 20900
Cortinovis Diego Luigi, 0392336040, diegoluigi.cortinovis@irccs-sangerardo.it
- Not yet recruiting
IOV Istituto Oncologico Veneto IRCCS
Padova, 35128
Pasello Giulia, 0498215608, giulia.pasello@iov.veneto.it
- Not yet recruiting
Azienda Ospedaliero-Universitaria di Parma
Parma, 43126
Tiseo Marcello, 0521702316, mtiseo@ao.pr.it
- Not yet recruiting
Azienda Ospedaliera di Perugia
Perugia, 06129
Metro Giulio, 0755783695, giulio.metro@ospedale.perugia.it
- Not yet recruiting
Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
Udine, 33010
Giacomo Pellizzari, 0432552754, giacomo.pelizzari@asufc.sanita.fvg.it
About this study
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.
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.
Read the 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.
- Being tested
- Lorlatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lorlatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 60 months
Secondary outcomes (3)
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.
Measured: Up to 60 months
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.
Measured: Up to 60 months
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.
Measured: Up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start15 Mar 2024
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro di Riferimento Oncologico - Aviano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06378892
- Sponsor's protocol ID
- CRO-2023-78
- Acronym
- ALK-PPL
- Status last verified
- Apr 2024
- First submitted
- 10 Apr 2024
- Last updated
- 23 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT06378892
- Acronym / sponsor ID
- ALK-PPL / CRO-2023-78
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Centro di Riferimento Oncologico - AvianoUniversity, hospital or other
- Study start
- 15 Mar 2024 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 23 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lorlatinib | Experimental | Drug: LorlatinibLorlatinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LorlatinibPlatinum-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. | Drug | Lorlatinib |
Primary outcome
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
PFS defined as the time from study enrollment to the first documented disease progression or death due to any cause, whichever occurs first.
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer Metastatic and ALK Gene Mutation, run by Centro di Riferimento Oncologico - Aviano at 9 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alessandra Bearz (0434-659294, abearz@cro.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2024.