A randomized, multicenter, open-label Phase III study of Lurbinectedin as monotherapy or Lurbinectedin in combination with Irinotecan compared to the preference of the investigator (Topotecan or Irinotecan) in patients with recurrent small cell lung cancer (SCLC) (LAGOON study).
Résumé de l'étude
Reason for the study: You are suffering from small cell lung cancer (Small-Cell Lung Cancer, SCLC) and are being treated with a standard therapy, but your cancer is not responding well to the previous treatment. The above-mentioned sponsor of the study is currently developing a new therapy. For this reason, the investigational drug called Lurbinectedin (alone or in combination with Irinotecan) is being tested in the study compared to a control group of Topotecan or Irinotecan. The sponsor wants to find out if the investigational drug can also be used to treat SCLC and may have advantages over standard therapy and whether the investigational drug is safe. The investigational drug being tested: Lurbinectedin is still in clinical trials and is not yet approved for your treatment in the European Union. Lurbinectedin was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with SCLC whose disease progresses after first-line treatment. Topotecan is a drug approved in the European Union and other countries for various types of solid tumors, including SCLC. Topotecan is frequently used to treat SCLC patients. Irinotecan is a drug recommended in the major medical guidelines (National Comprehensive Cancer Network guidelines) for the treatment of SCLC. Study procedures: If you choose to participate, you will be "randomized" into one of three treatment arms. Randomization means that you will be assigned to an arm by chance. Once the assignment has been made, it cannot be changed. You also cannot be randomized again.
(BASEC)
Intervention étudiée
Group A (Lurbinectedin alone):
You will receive Lurbinectedin 3.2 mg/m2, administered as an (i.v.) infusion over 60 minutes. This treatment will be repeated every three weeks (three weeks = one treatment cycle). You will receive Lurbinectedin through a peripheral catheter (a tube inserted into a vein in your arm) or through a central catheter (a tube inserted into a large vein in your neck or chest).
Group B (Lurbinectedin plus Irinotecan):
Irinotecan is a drug recommended by the major medical guidelines for the treatment of SCLC. This treatment will be repeated every three weeks (three weeks = one treatment cycle). You will receive both medications, Lurbinectedin and Irinotecan, through a central catheter or a peripheral catheter.
Group C (Control arm: Topotecan or Irinotecan)
Topotecan is used as a comparator drug since it is the current standard treatment for recurrent SCLC.
o Topotecan is administered either as an i.v. infusion over 30 minutes or orally. Topotecan is given for five consecutive days and the treatment is repeated every three weeks (three weeks = one treatment cycle). The Topotecan dose depends on how well your kidneys are functioning (from your kidney function).
Alternatively, Irinotecan is used as a comparator drug because the drug is recommended in the major medical guidelines (National Comprehensive Cancer Network guidelines) for the treatment of SCLC.
o Irinotecan 350 mg/m2, administered as an i.v. infusion over 90 minutes. This treatment will be repeated every three weeks (three weeks = one treatment cycle). You will receive Irinotecan through a central catheter or a peripheral catheter.
(BASEC)
Maladie en cours d'investigation
SCLC - recurrent small cell lung cancer
(BASEC)
1) Voluntary written consent of the patient before study-specific examinations take place 2) Age greater than or equal to 18 3) Confirmed diagnosis of small cell lung cancer 4) A previous platinum-based chemotherapy with/without anti-PD-1 or anti-PD-L1 5) Chemotherapy-free interval of greater than or equal to 30 days 6) Patients with CNS metastases may participate if it is confirmed that they have been pretreated and are radiologically stable 7) Adequate renal function, liver function, metabolic and hematological function 8) At least three weeks since the last previous antineoplastic treatment and recovery to grade ≤ 1 from an adverse event (AE) related to a previous cancer treatment 10) Previous radiotherapy (RT): At least two weeks after completion of prophylactic cranial irradiation (PCI) and at any other site not previously specified. 11) Evidence of non-childbearing desire in women of childbearing potential (BASEC)
Critères d'exclusion
1) Platinum-naive patients or patients who have been pretreated with more than one chemotherapy 2) Previous treatment with Lurbinectedin, Trabectedin, PM14 or topoisomerase I inhibitors (Irinotecan, Topotecan, etc.). 3) Active or untreated CNS metastases and/or carcinomatous meningitis. 4) Patients with a limited disease stage who must have been offered the option of local or regional treatment, including PCI, thoracic RT or both, prior to enrollment in the study, and the treatment must have been completed or declined 5) Comorbidities/concomitant medications: a) History of unstable angina, myocardial infarction, heart failure, or clinically significant valvular heart disease within the past year b) Symptomatic arrhythmia or unstable arrhythmia requiring treatment c) Existing alcohol consumption or liver cirrhosis d) Known Gilbert syndrome e) Existing uncontrolled infection. Severe non-healing wounds, ulcers, or bone fractures. Existing external drainages f) Persistent chronic liver disease requiring treatment of any origin. Hepatitis B, Hepatitis C. Subjects taking hepatitis-related antiviral therapy within six months prior to the first dose of study drugs will also be excluded. g) Interrupted or ongoing oxygen therapy within the last two weeks prior to enrollment. Patients with confirmed or suspected diffuse interstitial lung disease or pulmonary fibrosis h) Patients with a second invasive malignancy treated with chemotherapy and/or radiotherapy. Patients with a previous malignant disease completely removed three or more years before randomization, except treated in situ cervical carcinoma, basal or squamous cell carcinoma of the skin, and in situ transitional cell carcinoma of the bladder that has been continuously in remission since then, are allowed. i) Impairment of the patient's ability to adhere to treatment or follow the protocol. j) Documented or suspected fungal infections requiring systemic treatment within 12 weeks prior to randomization. k) Known infection with the Human Immunodeficiency Virus (HIV). l) Any previous or current chronic inflammatory bowel and/or liver disease, previous bowel obstruction or paralysis. m) Obvious symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or pericardial effusion, that increases rapidly and/or requires immediate local treatment within seven days. n) Any other serious illness that, in the investigator's judgment, significantly increases the risk associated with the patient's participation in this study (e.g., COVID-19 disease). 6) Radiotherapy in more than 35% of the bone marrow. 7) History of previous bone marrow and/or stem cell transplantation and allogeneic transplantation. 8) The patient has received a live vaccine or a live attenuated vaccine within 30 days prior to the first dose. The administration of inactivated vaccines is allowed. 9) Upcoming necessary radiotherapy 10) Existing allergy or hypersensitivity to the study medication or the excipients contained 11) Pregnant or breastfeeding women and fertile patients for whom it is not possible to use an effective method of contraception. (BASEC)
Lieu de l’étude
Bâle, Bellinzona, Lausanne, Autre
(BASEC)
Villars-sur-Glane Münsterlingen/Frauenfeld
(BASEC)
Sponsor
Pharma Mar AG - c/o OBC Suisse AG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Luis Mora
+34 91 846 60 00
regulatory@clutterpharmamar.comPharmaMar S.A.
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique du Vaud
(BASEC)
Date d'approbation du comité d'éthique
17.07.2023
(BASEC)
Identifiant de l'essai ICTRP
NCT05153239 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Randomized, Multicenter, Open-label, Phase III Study of Lurbinectedin Single-Agent or Lurbinectedin in Combination with Irinotecan versus Investigator’s Choice (Topotecan or Irinotecan) in Relapsed Small Cell Lung Cancer (SCLC) Patients (LAGOON Trial) (BASEC)
Titre académique
A Randomized, Multicenter, Open-label, Phase III Study of Lurbinectedin Single-Agent or Lurbinectedin in Combination With Irinotecan Versus Investigator's Choice (Topotecan or Irinotecan) in Relapsed Small Cell Lung Cancer Patients (LAGOON Trial) (ICTRP)
Titre public
Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON) (ICTRP)
Maladie en cours d'investigation
Relapsed Small Cell Lung Cancer (ICTRP)
Intervention étudiée
Drug: IrinotecanDrug: LurbinectedinDrug: IrinotecanDrug: TopotecanDrug: Lurbinectedin (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
1. Voluntary written informed consent of the patient obtained before any study-specific
procedure
2. Age>=18 years
3. Histologically or cytologically confirmed diagnosis of SCLC.
4. One prior line of platinum-containing chemotherapy with/without anti-PD-1 or
anti-PD-L1 (Note: at least 70% of patients included in the study have to be
pretreated with anti-PD-1 or anti-PD-L1)
5. Chemotherapy-free interval (CTFI, time from the last dose of first-line
platinum-containing chemotherapy to the occurrence of progressive disease) >= 30 days
(independent of the immunotherapy maintenance, if applicable)
6. Patients with history of Central Nervous System (CNS) metastases can participate
provided they are pretreated and radiologically stable (i.e., without evidence of
progression) for at least 4 weeks by repeated imaging (note: repeated imaging should
be performed during study screening), asymptomatic, and without requirement of
steroid treatment for at least 7 days before the first dose of study treatment
7. Eastern Cooperative Oncology Group (ECOG) PS <= 2
8. Adequate hematological, renal, metabolic and hepatic function:
1. Hemoglobin >= 9.0 g/dL [patients may have received prior red blood cell (RBC)
transfusion, if clinically indicated] absolute neutrophil count (ANC) >= 2.0 x
10^9/L, and platelet count >= 100 x 10^9/L.
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3.0 x
upper limit of normal (ULN).
3. Total bilirubin <= 1.5 x ULN or direct bilirubin <= ULN.
4. Albumin >= 3.0 g/dL.
5. Calculated creatinine clearance (CrCL) >= 30 mL/min (using Cockcroft and Gault's
formula).
9. At least three weeks since last prior antineoplastic treatment and recovery to grade
<= 1 from any adverse event (AE) related to previous anticancer treatment (excluding
sensory neuropathy, immune-related hypothyroidism, anemia, asthenia and alopecia,
all grade <= 2) according to the National Cancer InstituteCommon Terminology Criteria
for Adverse Events (NCICTCAE) v.5.
10. Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial
irradiation (PCI), and to any other site not previously specified.
11. Evidence of non-childbearing status for women of childbearing potential (WOCBP).
WOCBP must agree to use a highly effective contraceptive measure up to seven months
after treatment discontinuation. Fertile male patients with WOCBP partners should
use condoms during treatment and for four months following the last investigational
medicinal product (IMP) dose.
Exclusion Criteria:
1. Platinum-nave patients or patients pretreated with more than one prior chemotherapy
regimen (including patients re-challenged with same initial regimen).
2. Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors
(irinotecan, topotecan, etc.).
3. Active or untreated CNS metastases and/or carcinomatous meningitis.
4. Patients with limited-stage disease who are candidates for local or regional
therapy, including PCI, thoracic RT or both, must have been offered that option and
completed treatment or refused it prior to randomization.
5. Concomitant diseases/conditions:
1. History or presence of unstable angina, myocardial infarction, congestive heart
failure, or clinically significant valvular heart disease within last year.
2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing
treatment.
3. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
4. Known Gilbert's disease.
5. Active uncontrolled infection. Serious non-healing wound, ulcer or bone
fracture. Presence of external drainages.
6. Ongoing, treatment-requiring, non-neoplastic chronic liver disease of any
origin. For Hepatitis B, this includes positive tests for both Hepatitis B
surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction
(PCR). For Hepatitis C, this includes positive tests for both Hepatitis C
antibody and quantitative Hepatitis C PCR. Subjects taking hepatitis related
antiviral therapy within six months prior to the first dose of study drugs will
also be excluded.
7. Intermittent or continuous oxygen requirement within two weeks prior to
randomization. Patients with confirmed or suspected diagnosis of diffuse
interstitial lung disease or pulmonary fibrosis.
8. Patients with a second invasive malignancy treated with chemotherapy and/or RT.
Patients with a previous malignancy that was completely resected with curative
intention three or more years prior to randomization, except treated in situ
carcinoma of the cervix, basal or squamous cell skin carcinoma, and in situ
transitional cell bladder carcinoma and who has been continuously in remission
since then will be permitted.
9. Limitation of the patient's ability to comply with the treatment or to follow
the protocol.
10. Documented or suspected invasive fungal infections requiring systemic treatment
within 12 weeks of randomization.
11. Known human immunodeficiency virus (HIV) infection.
12. Any past or present chronic inflammatory colon and/or liver disease, past
intestinal obstruction, pseudo or subocclusion or paralysis.
13. Evident symptomatic pleural or cardiac effusion rapidly increasing and/or
necessitating prompt local treatment within seven days.
14. Any other major illness that, in the Investigator's judgment, will
substantially increase the risk associated with the patient's participation in
this study (e.g. COVID-19 disease).
6. RT in more than 35% of the bone marrow.
7. History of previous bone marrow and/or stem cell transplantation and allogenic
transplant.
8. Patient has received a live or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of inactivated vaccines is allowed.
9. Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord
compression).
10. History of allergy or hypersensitivity to any of the study drugs or any of their
excipients.
11. Women who are pregnant or breast feeding and fertile patients (men and women) who
are not able to use a highly effective method of contraception (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Overall survival (ICTRP)
Progression-free survival by IRC (Independent Review Committee);Progression-free survival by IA (Investigator Assessment);Overall response rate by IRC;Overall response rate by IA;Overall survival rate at 12 months;Overall survival rate at 24 months;Progression-free survival rate at 6 months by IRC;Progression-free survival rate at 6 months by IA;Progression-free survival rate at 12 months by IRC;Progression-free survival rate at 12 months by IA;Duration of response by IRC;Duration of response by IA;Patient-reported outcomes (ICTRP)
Date d'enregistrement
29.11.2021 (ICTRP)
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Jos? Antonio Lopez-Vilari?o, MD, jalopez-vilarino@pharmamar.com, 0034 91 823 4564 (ICTRP)
ID secondaires
PM1183-C-008-21 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT05153239 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible