Informations générales (source: ClinicalTrials.gov)
A Phase II Single-group Assignment, Multicenter Study of Efficacy and Safety of Lorlatinib Monotherapy After Failure of First-line Tyrosine Kinase Inhibitor in Patients with Advanced ROS1-positive Non-small Cell Lung Cancer (ALBATROS)
Interventional
Phase 2
Intergroupe Francophone de Cancerologie Thoracique (Voir sur ClinicalTrials)
mars 2021
janvier 2026
17 octobre 2024
ROS1 rearrangements are present in 1-2% of NSCLC cases and define a distinct molecular
subgroup. Like ALK (anaplastic lymphoma kinase) rearrangements in NSCLC, ROS1 fusions
confer sensitivity to the inhibitor crizotinib. Crizotinib, which is a tyrosine kinase
inhibitor (TKI), has been shown to be effective in tumors in several retrospective
studies.
Recently the FDA approved entrectinib for the treatment of patients with ROS1-positive
metastatic NSCLC. This indication is based on the results of pooled data from several
trials. Together, these studies demonstrate the efficacy for entrectinib across a variety
of solid tumor types including NSCLC with ROS1 fusion.
However, despite the efficacy of crizotinib or entrectinib in ROS1-positive NSCLC,
patients will develop resistance to these tyrosine kinase inhibitors.
Lorlatinib is a new and potent ROS1 / ALK inhibitor optimized to penetrate the
blood-brain barrier. A recent study has investigated the activity of lorlatinib against
the crizotinib-resistant ROS1G2032R mutation. In this situation, lorlatinib effectively
inhibited the catalytic activity of recombinant ROS1G2032R resulting in an
antiproliferative response. Because of its potency as an ROS1 inhibitor and its ability
to suppress the resistant ROS1 mutations, lorlatinib could be a treatment of choice in
ROS1-positive NSCLC.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL FOCH | HELENE DOUBRE | 21/10/2024 07:07:19 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Bichat | Valérie Gounant, Dr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Cochin | Marie Wislez, Pr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Tenon | Jacques Cadranel, Pr | Contact (sur clinicalTrials) | |||
| CHI DE CRETEIL | Isabelle Monnet, Dr | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT CURIE | Marie-Ange MASSIANI, Dr | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Angers - CHU - Angers - France | Marie Capucine Willemin, Dr | Contact (sur clinicalTrials) | |||
| Annecy - CH - Annecy - France | Dorine TEMPLEMENT, Dr | Contact (sur clinicalTrials) | |||
| Antony - Hôpital privé - Antony - France | Stanislas ROPERT, Dr | Contact (sur clinicalTrials) | |||
| AP-HP Hôpital Ambroise Paré - 92104 - Boulogne - France | Coraline Dumenil, Dr | Contact (sur clinicalTrials) | |||
| Avignon - CH - Avignon - France | Nicolas CLOAREC, Dr | Contact (sur clinicalTrials) | |||
| Bordeaux - CHU - Bordeaux - France | Maéva ZYSMAN, Dr | Contact (sur clinicalTrials) | |||
| Bordeaux - Institut Bergonie - Bordeaux - France | Sophie COUSIN, Dr | Contact (sur clinicalTrials) | |||
| Bordeaux - Polyclinique - Bordeaux - France | Sigolène GALLAND, Dr | Contact (sur clinicalTrials) | |||
| Caen - CHU Côte de Nacre - 14000 - Caen - France | Jeannick MADELAINE, Dr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier - Pneumologie - 72000 - Le Mans - France | Olivier Molinier, Dr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de la Côte Basque - 64100 - Bayonne - France | Sophie Schneider, Dr | Contact (sur clinicalTrials) | |||
| Centre Hospitalier du Pays d'Aix - 13616 - Aix-en-Provence - France | Stéphanie Martinez, Dr | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69373 - Lyon - France | Aurélie Swalduz, Dr | Contact (sur clinicalTrials) | |||
| Centre Paul Papin - 49055 - Angers - France | Frédéric BIGOT, Dr | Contact (sur clinicalTrials) | |||
| Chauny - CH - Chauny - France | Patrick DUMONT, Dr | Contact (sur clinicalTrials) | |||
| Cholet - CH - Cholet - France | Philippe MASSON, Dr | Contact (sur clinicalTrials) | |||
| CHRU Grenoble - Grenoble - France | Denis MORO-SIBILOT | Contact (sur clinicalTrials) | |||
| CHU Bretonneau - 37044 - Tours - France | Delphine Carmier, Dr | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Pneumologie - Toulouse - France | Audrey Rabeau, Dr | Contact (sur clinicalTrials) | |||
| Clermont-Ferrand - CHU - Clermont-Ferrand - France | Patrick MERLE, Dr | Contact (sur clinicalTrials) | |||
| Colmar - CH - Colmar - France | Lionel MOREAU | Contact (sur clinicalTrials) | |||
| Dijon - CRLCC - Dijon - France | Laure FAVIER, dR | Contact (sur clinicalTrials) | |||
| GRH Mulhouse Sud-Alsace - Mulhouse - France | Didier DEBIEUVRE, Dr | Contact (sur clinicalTrials) | |||
| Hôpital Calmette - 59037 - Lille - France | Alexis Cortot, Pr | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13273 - Marseille - France | Anne Madroszyk, Dr | Contact (sur clinicalTrials) | |||
| Lyon - URCOT - Pierre-Bénite - France | Michael Duruisseaux, Dr | Contact (sur clinicalTrials) | |||
| Marseille Hôpital Nord - 13915 - Marseille - France | Pascale Tomasini, Dr | Contact (sur clinicalTrials) | |||
| Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg - 67091 - Strasbourg - France | Céline Mascaux, Pr | Contact (sur clinicalTrials) | |||
| Rouen - CHU - Rouen - France | Florian GUISIER, Dr | Contact (sur clinicalTrials) | |||
| Valenciennes - Clinique - Valenciennes - France | Hélène MEYER, Dr | Contact (sur clinicalTrials) | |||
| Vandoeuvre-lès-Nancy - CHU - Vandœuvre-lès-Nancy - France | Aurélien BRINDEL, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Signed Written Informed Consent: Subjects must have signed and dated an IRB/IEC
approved written informed consent form in accordance with regulatory and
institutional guidelines. This must be obtained before the performance of any
protocol related procedures that are not part of normal subject care. Subjects must
be willing and able to comply with scheduled visits, treatment schedule, and
laboratory testing
- Patients with histologically or cytologically confirmed diagnosis of locally
advanced not eligible to a local treatment or metastatic NSCLC (Stage IIIB, IIIC or
IV accordingly to 8th classification TNM, UICC 2015) that carries an ROS1
rearrangement, as determined by the molecular biology platform of the investigator
by FISH assay or by Immunohistochemistry (IHC), or Next Generation Sequencing (NGS)
or RNA sequencing approach.
- Disease Status Requirements: Disease progression meeting RECISTv1.1 after one prior
line of treatment with crizotinib or entrectinib (+ one line of chemotherapy with or
without immunotherapy before TKI treatment).
Note: patient with disease progression after treatment with another ROS1-TKI may still be
eligible upon discussion with IFCT.
- Tumor Requirements: All Patients must have at least one measurable target lesion
according to RECIST v1.1. The radiological assessment has to be done within the
timelines indicated. In addition, patients with asymptomatic and neurologically
stable CNS metastases (including patients controlled with stable or decreasing
steroid use within the last week prior to study entry) will be eligible. The brain
metastases may be newly diagnosed after disease progression with crizotinib or
entrectinib or be present as progressive disease after surgery, whole brain
radiotherapy or stereotactic radiosurgery (see Exclusion Criterion for the lapsed
time period required between the end of radiotherapy and study entry). Patients who
have leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible
if the LM/CM is visualized on MRI or if documented baseline cerebral spinal fluid
(CSF) positive cytology is available and asymptomatic and neurologically stable
(including patients controlled with stable or decreasing steroid use within the last
week prior to study entry).
- Tumor Sample Requirement: Tumour biopsy sampling on fresh tissue (FFPE blocks
required) obtained after progression on crizotinib or entrectinib. Tumour biopsy
should be exploitable for molecular analysis. If the tumour biopsy is not
exploitable, the inclusion will be allowed if two blood samples are provided for
tumoral cfDNA analysis. The Sponsor will monitor a posteriori the exploitability of
provided tumour biopsies and will investigate the impossibility to perform or repeat
tissue tumor sampling.
- Age ≥18 years.
- Life expectancy of at least 12 weeks, in the opinion of the Investigator.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
- Adequate Bone Marrow Function, including: Absolute Neutrophil Count (ANC) ≥1.5 x
109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL.
- Adequate Pancreatic Function, including: Serum lipase ≤1.5 x ULN.
- Adequate Renal Function, including: Serum creatinine ≤1.5 x ULN or estimated
creatinine clearance ≥45 mL/min as calculated using the method standard for the
institution.
- Adequate Liver Function, including: Total serum bilirubin ≤1.5 x ULN; Aspartate
Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if
there is liver metastases involvement.
- Participants must have recovered from treatment toxicities to CTCAE Grade ≤ 1 (for
participants who have developed interstitial lung disease [ILD], they must have
fully recovered) except for AEs that in the investigator' judgment do not constitute
a safety risk for the patient.
- Participants must have recovered from effects of any major surgery, or significant
traumatic injury, at least 35 days before the first dose of lorlatinib
- For all females of childbearing potential, a negative pregnancy test must be
obtained within the screening period. A patient is of childbearing potential if, in
the opinion of the investigator, she is biologically capable of having children and
is sexually active. Additionally, all females of childbearing potential must provide
an agreement to remain abstinent or use two adequate methods of contraception,
including at least one method with a failure rate of < 1% per year, during the
treatment period and for at least 90 days after the last dose of study drug.
- For men: agreement to remain abstinent or use an effective method of contraception
(e.g., condom) during the treatment period and for at least 14 weeks after the last
dose of study drug and agreement to refrain from donating sperm during this same
period.
- Evidence of a personally signed and dated informed consent document indicating that
the patient has been informed of all pertinent aspects of the study.
- Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedure.
- Participant has national health insurance coverage.
- Washout period: if previous progression on ROS1-TKI: 7 days from last dose of the
drug. The washout period may be shortened to 2 days at investigator discretion.
- Signed Written Informed Consent: Subjects must have signed and dated an IRB/IEC
approved written informed consent form in accordance with regulatory and
institutional guidelines. This must be obtained before the performance of any
protocol related procedures that are not part of normal subject care. Subjects must
be willing and able to comply with scheduled visits, treatment schedule, and
laboratory testing
- Patients with histologically or cytologically confirmed diagnosis of locally
advanced not eligible to a local treatment or metastatic NSCLC (Stage IIIB, IIIC or
IV accordingly to 8th classification TNM, UICC 2015) that carries an ROS1
rearrangement, as determined by the molecular biology platform of the investigator
by FISH assay or by Immunohistochemistry (IHC), or Next Generation Sequencing (NGS)
or RNA sequencing approach.
- Disease Status Requirements: Disease progression meeting RECISTv1.1 after one prior
line of treatment with crizotinib or entrectinib (+ one line of chemotherapy with or
without immunotherapy before TKI treatment).
Note: patient with disease progression after treatment with another ROS1-TKI may still be
eligible upon discussion with IFCT.
- Tumor Requirements: All Patients must have at least one measurable target lesion
according to RECIST v1.1. The radiological assessment has to be done within the
timelines indicated. In addition, patients with asymptomatic and neurologically
stable CNS metastases (including patients controlled with stable or decreasing
steroid use within the last week prior to study entry) will be eligible. The brain
metastases may be newly diagnosed after disease progression with crizotinib or
entrectinib or be present as progressive disease after surgery, whole brain
radiotherapy or stereotactic radiosurgery (see Exclusion Criterion for the lapsed
time period required between the end of radiotherapy and study entry). Patients who
have leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible
if the LM/CM is visualized on MRI or if documented baseline cerebral spinal fluid
(CSF) positive cytology is available and asymptomatic and neurologically stable
(including patients controlled with stable or decreasing steroid use within the last
week prior to study entry).
- Tumor Sample Requirement: Tumour biopsy sampling on fresh tissue (FFPE blocks
required) obtained after progression on crizotinib or entrectinib. Tumour biopsy
should be exploitable for molecular analysis. If the tumour biopsy is not
exploitable, the inclusion will be allowed if two blood samples are provided for
tumoral cfDNA analysis. The Sponsor will monitor a posteriori the exploitability of
provided tumour biopsies and will investigate the impossibility to perform or repeat
tissue tumor sampling.
- Age ≥18 years.
- Life expectancy of at least 12 weeks, in the opinion of the Investigator.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
- Adequate Bone Marrow Function, including: Absolute Neutrophil Count (ANC) ≥1.5 x
109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL.
- Adequate Pancreatic Function, including: Serum lipase ≤1.5 x ULN.
- Adequate Renal Function, including: Serum creatinine ≤1.5 x ULN or estimated
creatinine clearance ≥45 mL/min as calculated using the method standard for the
institution.
- Adequate Liver Function, including: Total serum bilirubin ≤1.5 x ULN; Aspartate
Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if
there is liver metastases involvement.
- Participants must have recovered from treatment toxicities to CTCAE Grade ≤ 1 (for
participants who have developed interstitial lung disease [ILD], they must have
fully recovered) except for AEs that in the investigator' judgment do not constitute
a safety risk for the patient.
- Participants must have recovered from effects of any major surgery, or significant
traumatic injury, at least 35 days before the first dose of lorlatinib
- For all females of childbearing potential, a negative pregnancy test must be
obtained within the screening period. A patient is of childbearing potential if, in
the opinion of the investigator, she is biologically capable of having children and
is sexually active. Additionally, all females of childbearing potential must provide
an agreement to remain abstinent or use two adequate methods of contraception,
including at least one method with a failure rate of < 1% per year, during the
treatment period and for at least 90 days after the last dose of study drug.
- For men: agreement to remain abstinent or use an effective method of contraception
(e.g., condom) during the treatment period and for at least 14 weeks after the last
dose of study drug and agreement to refrain from donating sperm during this same
period.
- Evidence of a personally signed and dated informed consent document indicating that
the patient has been informed of all pertinent aspects of the study.
- Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedure.
- Participant has national health insurance coverage.
- Washout period: if previous progression on ROS1-TKI: 7 days from last dose of the
drug. The washout period may be shortened to 2 days at investigator discretion.
- Participants with disease progression on front-line treatment with TKI i.e.
crizotinib or entrectinib limited to CNS or one non-CNS site (oligo-metastasis) and
eligible to a local ablative treatment (surgery or stereotaxic radiotherapy).
- Histological transformation with neuro-endocrine differentiation.
- Spinal cord compression is excluded unless the patient demonstrates good pain
control attained through therapy and there is stabilization or recovery of
neurological function for the 4 weeks prior to study entry.
- Patients with symptomatic and neurologically instable CNS metastases or
leptomeningeal metastasis (including patients that require increasing doses of
steroids within one week prior to Day 0 of screening phase and during the screening
phase to manage CNS symptoms).
- Major surgery within 35 days of study entry. Minor surgical procedures (eg, port
insertion, mediastinoscopy, surgical procedure for re-sampling) are not excluded,
but sufficient time at investigator discretion should have passed for wound healing.
- Radiation therapy within 2 weeks of study entry (except palliative to relieve bone
pain). Palliative radiation (≤15 fractions) must have been completed at least 48
hours prior to study entry. Stereotactic or small field brain irradiation must have
completed at least 2 weeks prior to study entry. Whole brain radiation must have
completed at least 4 weeks prior to study entry.
- Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation
or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137, or anti-CTLA-4.
- Active and clinically significant bacterial, fungal, or viral infection including
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or
acquired immunodeficiency syndrome (AIDS)-related illness.
- Clinically significant cardiovascular disease (that is, active or <3 months prior to
enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable
angina, congestive heart failure (New York Heart Association Classification Class ≥
II), second-degree or third-degree AV block (unless paced) or any AV block with PR
>220 msec.
- Ongoing cardiac dysrhythmias of 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, athletic patients etc.), machine-read ECG with QTc
>470 msec, or congenital long QT syndrome.
- Patients with predisposing characteristics for acute pancreatitis according to
investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease,
alcoholism [more than 4 drinks on any day or 14 drinks per week where 1 drink is
defined as the alcoholic beverage containing approximately 14 grams of pure alcohol,
eg, 12 fl oz/360 mL regular beer or 5 fl oz/150 mL of wine] in the last month.
- History of bilateral or Grade 3 or 4 interstitial fibrosis or diffuse interstitial
lung disease. Patients with history of prior radiation pneumonitis are not excluded.
- Other severe acute or chronic medical or psychiatric condition, including recent
(within the past year) or active suicidal ideation or behavior, 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
inappropriate for entry into this study.
- Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer,
in situ cervical cancer, papillary thyroid cancer, DCIS of the breast or localized
and presumed cured prostate cancer) within the last 3 years.
- Active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic
diverticular disease or previous gastric resection or lap band.
- Current use or anticipated need for food or drugs prohibited (see chapter 7.9 for
details).
- Patients presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by
echocardiogram or Multi-Gated Acquisition Scan (MUGA) according to institutional
lower limits.
- Breastfeeding female patients (including patients who intend to interrupt
breastfeeding).
- Liver disease characterized by: ALT or AST level > 3 the upper normal limit (UNL) (≥
5 x UNL for patients with liver metastases) confirmed on 2 consecutive measures OR
impaired excretory function (e.g.. hyperbilirubinemia) or synthetic function or
other conditions of decompensated liver disease e.g.: coagulopathy, Hepatic
encephalopathy, hypoalbuminemia, ascites and bleeding from esophageal varices OR
Acute viral or autoimmune or other types of hepatitis.