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Non Small Cell Lung CancerPhase 2ALKALINENCT04127110

Activity of Lorlatinib Based on ALK Resistance Mutations Detected on Blood in ALK Positive NSCLC Patients

A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 26 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study includes patients diagnosed with a metastatic non small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) translocation. The standard treatment for patients with metastatic non small cell lung cancer with ALK translocation is represented by personalized treatment with drugs called ALK… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Lorlatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
26 sitesin 7 countries
Study dates
17 Nov 2020to Nov 2024
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

  • Age ≥18 years old
  • Histologically or cytologically confirmed diagnosis of NSCLC with ALK rearrangement, assessed by fluorescence in situ hybridization (FISH) assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc) approved by food and drug administration (FDA)
  • Stage IIIB (not eligible for local therapy) or stage IV (according to Union for International Cancer Control (UICC) tumor lymph node metastasis (TNM) staging v8.0)
  • World health organization (WHO) performance status (WHO PS) of 0-2
  • Previous treatment with at least one 2nd-generation ALK inhibitor. The 2nd-generation ALK TKI (ceritinib, alectinib, brigatinib) should be the latest therapy.
  • Progressive disease during treatment with 2nd-generation ALK inhibitor prior to the administration of lorlatinib
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  • Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvis and brain MRI performed within 28 days prior to study enrolment
  • Note: At least one measurable extracranial lesion is required.
  • Archival tissue from primary tumour or metastatic site, if available, and blood samples
  • Note: if blood samples cannot be collected (patient's refusal or any other reason), patient will not be eligible for this study.
  • Treated and/or untreated brain or leptomeningeal metastases will be allowed if asymptomatic and/or controlled (stable dose of steroids 7 days before the beginning of lorlatinib treatment)
  • Adequate bone marrow and organ function defined as following:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L;
  • Platelets ≥ 100 x 10E9/L;
  • Hemoglobin ≥ 9 g/dL;
  • Serum total amylase ≤1.5 Upper Limit Normal (ULN);
  • Serum lipase ≤1.5 ULN;
  • Serum creatinine ≤1.5 x ULN or estimated creatinine clearance > 30 mL/min - Total serum bilirubin ≤1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN; for patients with Gilbert's disease total bilirubin may be > 1.5 x ULN, however direct bilirubin must be normal;
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5.0 x ULN if there is liver metastases involvement);
  • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to the first dose of lorlatinib.
  • Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression or other reasons.
  • Patients of childbearing / reproductive potential should use highly effective birth control measures, as defined by the investigator, during the study treatment period and for at least 5 weeks after the last dose of lorlatinib for female patients and for at least 14 weeks after the last dose of lorlatinib for male patients. A highly effective method of birth control is defined as a method, which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
  • Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomized partner
  • Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
  • Note: Lorlatinib can induce Cytochrome P450 3A4/5 (CYP3A4/5) both in vitro and in vivo. Most hormonal contraceptives are CYP3A substrates, therefore, if this method of contraception is chosen it must be used along with condom (male or female condom) due to the risk of contraception failure.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 7 days after the last dose of lorlatinib.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Who cannot join

  • Spinal cord compression. Patients who received adequate treatment (surgery or radiotherapy) and has adequate control of the pain and stabilization and/or recovery of neurological symptoms/function for the 3 weeks prior to study entry are allowed
  • Major surgery within 4 weeks prior to study enrolment. Complete wound healing from major surgery must have occurred 3 weeks before the first dose of study treatment.
  • Minor surgical procedures (including port insertion, uncomplicated tooth extractions) without complete wound healing at the latest 1 week before the first dose of study treatment.
  • Radiation therapy within 2 weeks of study entry. Exception are:
  • Palliative radiation (≤10 fractions) is allowed if completed at least 48 hours prior to study enrolment
  • Stereotactic or small field brain irradiation is allowed if completed at least 2 weeks prior to study enrolment
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  • Whole brain radiation is allowed if completed at least 4 weeks prior to study enrolment
  • Any systemic anti-cancer therapy or an investigational drug treatment completed within 5 half-lives prior to start lorlatinib (in case of clinically meaningful risk of tumour flare according to investigator's assessment, discussion with EORTC is required before enrolment)
  • Any unresolved toxicities from prior systemic therapy, including haematological toxicities, greater than International Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 2 at the time of study enrolment
  • Active infection requiring therapy
  • Known active hepatitis B (HBV) or hepatitis C (HCV). Active HBV is defined as a known positive hepatitis B surface antigen (HBsAg) result. Active HCV is defined by a known positive Hep C antibody (Ab) result and known quantitative HCV ribonucleic acid (RNA) result greater than the lower limits of detection of the assay
  • Known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness Note: Testing for HIV must be performed at sites where mandated locally
  • Any of the following cardiac criteria:
  • Clinically significant cardiovascular disease (that is active or occurred <3 months prior to enrolment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), second-degree or third-degree atrioventricular (AV) block (unless paced) or any AV block with PR >220 msec
  • Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.)
  • Abnormal Left Ventricular Ejection Fraction (LVEF): LVEF <50% (assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO))
  • History of interstitial lung disease (ILD) or history of (non-infectious) pneumonitis that required oral or intravenous (IV) steroids (other than Chronic obstructive pulmonary disease (COPD) exacerbation) or current pneumonitis or current evidence of interstitial lung disease. Patients with history of prior radiation pneumonitis are not excluded
  • Any serious or uncontrolled acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behaviour, chronic alcoholism, drug addiction, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient not eligible for this study
  • Hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
  • Inability to swallow and/or retain oral tablets or impaired gastrointestinal function or disease that may significantly alter the absorption of lorlatinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • Evidence of active hematologic or primary solid tumour malignancy (other than completely resected non-melanoma skin cancer, successfully treated in situ carcinoma for example in situ cervical cancer, completely resected and successfully treated papillary thyroid cancer, or localized and presumed cured prostate cancer) within the last 3 years
  • History of hypersensitivity to excipients of Lorlatinib (please refer to Summary of Product Characteristics - SmPC)
  • Patients currently receiving (or unable to stop use at least 3 plasma half-lives of the strong CYP3A4/5 inducer before lorlatinib treatment is started) medications or herbal supplements known ti be strong inducers of the cytochrome P450 (CYP) 3A4/5
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Important note: All eligibility criteria must be adhered to, in case of deviation a discussion with Headquarters and study coordinator is mandatory.

Trial locations and contacts

26 sites in 7 countries.

26 sites in 7 countries

Spain11 sites

  • Hospital Clinic Universitari de Barcelona

    Barcelona

  • Hospital De La Santa Creu I Sant Pau

    Barcelona

  • Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol

    Barcelona

  • Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Clinica Universidad de Navarra - Clinica Universitaria De Navarra

    Madrid

  • Hospital Universitario 12 De Octubre

    Madrid

  • Hospital Universitario Ramon y Cajal

    Madrid

  • Hospital Universitari Son Espases

    Palma de Mallorca

  • Clinica Universidad de Navarra - Clinica Universitaria De Navarra

    Pamplona

  • University Hospital Virgen del Rocio

    Seville

Other trials in Spain

France5 sites

  • Centre Hospitalier Avignon

    Avignon, 84902

  • Assistance Publique Hopitaux Paris - Hopital Avicenne

    Bobigny

  • CHU de Brest

    Brest, 29200

  • Centre Hopitalier Intercommunal De Creteil

    Créteil, 94010

  • Gustave Roussy

    Villejuif

Other trials in France

Belgium4 sites

  • Institut Jules Bordet-Hopital Universitaire ULB

    Brussels, 1000

  • Cliniques Universitaires Saint-Luc

    Brussels, BE 1200

  • Universitair Ziekenhuis Antwerpen

    Edegem, BE 2650

  • CHU-UCL Namur - CHU Mont Godinne - UCL Namur

    Yvoir, 5530

Other trials in Belgium

Netherlands3 sites

  • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

    Amsterdam, 1066 CX

  • Academisch Ziekenhuis Maastricht

    Maastricht

  • Erasmus MC

    Rotterdam

Other trials in Netherlands

Jordan1 site

  • King Hussein Cancer Center

    Amman

Other trials in Jordan

Norway1 site

  • Oslo University Hospital - Radiumhospitalet

    Oslo

Other trials in Norway

United Kingdom1 site

  • The Christie NHS Foundation Trust

    Manchester

Other trials in United Kingdom

About this study

Official title: Activity of Lorlatinib Based on ALK Resistance Mutations on Blood in ALK Positive NSCLC Patients Previously Treated With 2nd Generation ALK Inhibitor

This study includes patients diagnosed with a metastatic non small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) translocation. The standard treatment for patients with metastatic non small cell lung cancer with ALK translocation is represented by personalized treatment with drugs called ALK inhibitors. During the treatment with an ALK inhibitor, the tumour can start to grow again, because the tumour adapts to the drug and develops escape mechanisms, becoming resistant. At the tumour cells level, the mechanisms underlying resistance can include the development of other alterations, mainly mutations, including in the ALK gene. The alterations that developed depend on the drug the tumour has been exposed to.

The alterations can be identified by analysing tumour tissue obtained through a biopsy, however, repeating a tumour biopsy is difficult and risky and might not be able to provide sufficient tissue for the test. Therefore in the last years, new tests have been developed to identify the mutations in the blood.

Read more

Lorlatinib is a drug that inhibits ALK and has already been identified to be able to control the tumour growth when ALK mutations are identified and is already approved as standard treatment after progression to a previous treatment with ALK inhibitors.

The purpose of this study is to identify which patient populations may benefit most from treatment with lorlatinib, based on the alterations found in their genes.

Being tested
Lorlatinib
Keywords
Anaplastic lymphoma kinase (ALK) positive non small cell lung cancer (NSCLC)
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LorlatinibDrug

    Lorlatinib is administered orally at the daily dose of 100 mg (four tablets of 25 mg).

Study groups in NCT04127110
Study groupRoleWhat they receive
LorlatinibExperimentalLorlatinib is administered orally at the daily dose of 100 mg (four tablets of 25 mg). Lorlatinib will be taken continuously on a daily basis until disease progression, unacceptable toxicity, occurrence of any withdrawal criterion, whichever comes first.
Receives: Drug: Lorlatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    Progression Free Survival Rate at 12 months (PFSR-12) is defined as the proportion of patients at 12 months who are alive and non-progressing.

    Measured: 12 months after enrolment of last patient

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS is defined as the time interval between the date of enrolment and the date of death from any cause. If no event has been observed, then the patient is censored at the last date known to be alive.

    Measured: 12 months after enrolment of last patient

  2. Overall Response Rate (ORR)

    Overall Response Rate (ORR) is an overall rate including patients with documented complete response (CR) or partial response (PR)

    Measured: 12 months after enrolment of last patient

  3. Duration of Response (DOR)

    Duration of Response will only be reported for patients who achieved either CR or PR. The duration of response is measured from the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. If progression has not been observed, the patient will be censored at the date of the last follow up examination. In the event of death without progression competing risk method will be used.

    Measured: 12 months after enrolment of last patient

  4. CNS Overall Response Rate (CNS-ORR)

    CNS Overall Response Rate (CNS ORR) is an overall rate including patients with documented complete response (CNS-CR) or partial response (CNS-PR)

    Measured: 12 months after enrolment of last patient

  5. Safety profile according to NCI CTCAE v.5

    Safety profile according to NCI CTCAE v.5

    Measured: 30 days after last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2019
  2. Study start17 Nov 2020
  3. Primary completion31 Jul 2024
  4. Study completionNov 2024 (estimated)

Resources

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
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04127110
Sponsor's protocol ID
EORTC-1825
Other IDs
2019-003862-41, 2019
Acronym
ALKALINE
Status last verified
Nov 2024
First submitted
14 Oct 2019
Last updated
5 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lorlatinib in people with Non Small Cell Lung Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 26 sites in 7 countries.

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 33 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Spain, France, Belgium, Netherlands, Jordan and 2 more countries. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 12 months after enrolment of last patient). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04127110.

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 5 Nov 2024.

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