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)

PharmaMar (Industry)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of two experimental arms consisting of lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator's Choice (topotecan or irinotecan) as control arm (Group C), in Small-cell Lung Cancer (SCLC) patients who failed one prior platinum-containing line.

Detailed Description

Approximately 705 Adult SCLC patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 who have failed one prior platinum-containing line with CTFI ≥ 30 days and controlled asymptomatic Central Nervous System metastases will be enrolled and assigned to each treatment arm.

Central randomization will be implemented; patients will be assigned to each treatment arm at a 1:1:1 ratio.

An Independent Data Monitoring Committee (IDMC) will oversee the conduct of the study. The IDMC should have access to unblinded efficacy and safety data throughout the trial to enable timely and informed judgments about risks and benefits.

Study Design

Study Type:
Anticipated Enrollment :
705 participants
Intervention Model:
Parallel Assignment
Intervention Model Description:
Multicenter, open-label, randomized, controlledMulticenter, open-label, randomized, controlled
None (Open Label)
Primary Purpose:
Official Title:
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)
Actual Study Start Date :
Jul 22, 2022
Anticipated Primary Completion Date :
May 1, 2025
Anticipated Study Completion Date :
May 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lurbinectedin

Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)

Drug: Lurbinectedin
Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 q3wk
Other Names:
  • PM01183
  • Experimental: Lurbinectedin plus Irinotecan

    Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): Irinotecan (Day 1 and Day 8) Lurbinectedin (Day 1)

    Drug: Irinotecan
    Irinotecan 75 mg/m² intravenously Days 1 & 8 q3wk

    Drug: Lurbinectedin
    Lurbinectedin 2.0 mg/m² will be administered intravenously on Day 1 q3wk
    Other Names:
  • PM01183
  • Active Comparator: Control arm

    Best Investigator's choice prior to randomization between: Irinotecan on Day 1 q3wk Topotecan on Days 1-5 q3wk

    Drug: Irinotecan
    Irinotecan 350 mg/m² intravenously Day 1 q3wk

    Drug: Topotecan
    Topotecan 2.3 mg/m² oral or 1.5 mg/m² intravenously Days 1-5 q3wk

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival [From the date of randomization to the date of death or last contact, up to 39 months]

      Overall survival (OS) will be calculated from the date of randomization to the date of death or last contact (in this case, survival will be censored on that date).

    Secondary Outcome Measures

    1. Progression-free survival [From the date of randomization to the date of progressive disease, death or last tumor assessment or further anticancer treatment, up to 39 months]

      Progression-free survival (PFS) will be calculated from the date of randomization to the date of documented progression per RECIST v.1.1 (Progressive disease is declared when there is an increase in sum of target disease ≥ 20%) or death (regardless of the cause of death). If the patient receives further antitumor therapy, withdraws from the study, or is lost to follow-up before progressive disease (PD), PFS will be censored at the date of last evaluable tumor assessment before the date of subsequent antitumor therapy.

    2. Overall response rate [From the date of randomization to the date of death or last contact, up to 39 months]

      Overall response rate (ORR) will be the best response obtained in any evaluation according to RECIST v.1.1. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is > -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.

    3. Overall survival rate at 12 months [At 12 months]

      Overall survival rate at 12 months is defined as the percentage of people who are still alive at 12 months after randomization.

    4. Overall survival rate at 24 months [At 24 months]

      Overall survival rate at 24 months is defined as the percentage of people who are still alive at 24 months after randomization.

    5. Progression-free survival rate at 6 months [At 6 months]

      Progression-free survival rate at 6 months is defined as the percentage of people who remain free from progression at 6 months after randomization

    6. Progression-free survival rate at 12 months [At 12 months]

      Progression-free survival rate at 12 months is defined as the percentage of people who remain free from progression at 12 months after randomization

    7. Duration of response [From the date of first documentation of complete or partial response to the date of documented progression disease, death or last contact, up to 39 months]

      Duration of response (DoR) will be calculated from the date of first documentation of response per RECIST v.1.1 (complete or partial response, whichever occurs first) to the date of documented PD or death. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is > -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.

    8. Patient-reported outcomes [At baseline and every six weeks (± one week) until end of treatment, up to 39 months]

      To measure the quality of life of patients, the Lung Cancer Symptom Scale (LCSS) questionnaire will be analyzed.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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:

    9. 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 109/L, and platelet count ≥ 100 x 109/L.

    10. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).

    11. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN.

    12. Albumin ≥ 3.0 g/dL.

    13. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).

    14. 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, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer InstituteCommon Terminology Criteria for Adverse Events (NCICTCAE) v.5.

    15. Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.

    16. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six 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-naïve 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:

    6. History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.

    7. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.

    8. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.

    9. Known Gilbert's disease.

    10. Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.

    11. 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.

    12. 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.

    13. 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.

    14. Limitation of the patient's ability to comply with the treatment or to follow the protocol.

    15. Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.

    16. Known human immunodeficiency virus (HIV) infection.

    17. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.

    18. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.

    19. Active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).

    20. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.

    21. RT in more than 35% of the bone marrow.

    22. History of previous bone marrow and/or stem cell transplantation and allogenic transplant.

    23. Patient has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

    24. Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).

    25. History of allergy or hypersensitivity to any of the study drugs or any of their excipients.

    26. Women who are pregnant or breast feeding and fertile patients (men and women) who are not able to use an effective method of contraception

    Contacts and Locations


    Site City State Country Postal Code
    1 Duly Health and Care Joliet Illinois United States 60435
    2 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    3 FirstHealth Outpatient Cancer Center Pinehurst North Carolina United States 28374
    4 The Chris Obrien Lifehouse Camperdown New South Wales Australia 2050
    5 BRICC - Ballarat Health Services Ballarat Central Victoria Australia 3350
    6 Box Hill Hospital Eastern Health Clinical School Box Hill Victoria Australia 3128
    7 Antwerp University Hospital Edegem Antwerp Belgium 2650
    8 Algemeen Ziekenhuis AZ Klina - Borstkliniek Brasschaat Belgium 2930
    9 Grand Hopital de Charleroi GHdC - Hopital Saint Joseph Charleroi Belgium 6000
    10 Centre Hospitalier Chretien CHC - MontLegia Liège Belgium 4000
    11 CHR de la Citadelle Liège Belgium 4000
    12 CHU Liege Liège Belgium 4000
    13 Az Sint Maarten Mechelen Mechelen Belgium 2800
    14 Centre Hospitalier Universitaire (CHU) Ambroise Pare Mons Belgium 7000
    15 Multiprofile Hospital for Active Treatment - Uni Hospital OOD Department of Medical Oncology Sofia Dianabad Bulgaria 1797 NPZ
    16 Complex Oncology Center - Plovdiv EOOD, First Department of Medical Oncology and Oncological Diseases in Gastroenterology Plovdiv Bulgaria 4000
    17 Specialized hospital for active treatment of oncological diseases Sofia Bulgaria 1233
    18 Multiprofile Hospital for Active Treatment Serdika EOOD Second Department of Medical Oncology Sofia Bulgaria 1303
    19 McGill University Health Centre (MUHC) Montréal Canada H4A 3J1
    20 Hopital Jean Minjoz Besancon France 25030
    21 AssAP-HP - Hopital Ambroise-Pare Boulogne-Billancourt France 92100
    22 Hopital Morvan CHU de Brest Brest France 29200
    23 CHU de Caen - Hopital Cote de Nacre Caen France 14033
    24 Centre Hospitalier Intercommunal de Creteil (CHIC) Créteil France 94000
    25 APHM - Hopital Nord Marseille France 13015
    26 Gustave Roussy Villejuif France 94805
    27 High Technology Hospital Medcenter Batumi Georgia 6000
    28 Todua Clinic Tbilisi Georgia 112
    29 New Hospitals Tbilisi Georgia 114
    30 Institute Of Clinical Oncology Tbilisi Georgia 156
    31 JSC Evex Hospitals "Caraps Medline" Tbilisi Georgia 179
    32 LTD Cancer Research Centre Tbilisi Georgia 186
    33 LungenClinic Grosshansdorf Großhansdorf Schleswig Holstein Germany 22927
    34 Charite - Universitaetsmedizin Berlin Berlin Germany 13353
    35 Klinikum Bremen Ost Bremen Germany 28325
    36 Asklepios Fachklinik München-Gauting Gauting Germany 82131
    37 Krankenhaus Martha-Maria Halle gGmbH Halle (saale) Germany 06120
    38 Thoraxclinic Heidelberg GmbH Heidelberg Germany 69126
    39 Klinikum Kassel - Medizinische Klinik IV Kassel Germany 34125
    40 Universitaetsmedizin Mannheim Mannheim Germany 68167
    41 Staedtisches Klinikum München - Bogenhausen München Germany 81925
    42 A.O. SS. Antonio e Biagio e Cesare Arrigo di Alessandria Alessandria Italy 15121
    43 Clinica Oncologica Ancona Italy 60126
    44 IRCCS Centro di Riferimento Oncologico Aviano Italy 33081
    45 IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi Oncologia medica Bologna Italy 40138
    46 Azienda Ospedaliera Univ. Policlinico G Rodolico San Marco Catania Italy 95125
    47 A.O. Santa Croce e Carle, Ospedale Carle Cuneo Italy 12100
    48 AOU Careggi Florence Italy 50134
    49 ASL 3 Genovese Oncologia Medica Villa Scassi Genova Italy 16149
    50 Universita degli Studi della Campania Luigi Vanvitelli Napoli Italy 80138
    51 Azienda Ospedaliero-Universitaria San Luigi Gonzaga Orbassano Italy 10043
    52 Oncologia Medica II Istituto Oncologico Veneto IRCCS Padova Italy 35128
    53 Azienda USL di Piacenza Piacenza Italy 29121
    54 Irccs-Crob Rionero In Vulture Italy 85028
    55 IFO Regina Elena Roma Italy 00128
    56 Policlinico Uni. Campus Bio-Medico Roma Italy 00128
    57 Azienda Ospedaliera Univ. Senese Policlinico Le Scotte Siena Italy 53100
    58 ASST Valtellina e Alto Lario Ospedale di Sondrio ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio Sondrio Italy 23100
    59 ASST Sette Laghi Varese Italy 21100
    60 II Klinika Chorob Pluc i Gruzlicy Białystok Poland 15-569
    61 Szpitale Pomorskie Sp. z o.o., Oddzial Onkologii K Gdynia Poland 81-519
    62 Specjalistyczna Praktyka Lekarska Slawomir Mandziuka Lublin Poland 20-093
    63 Szpital Specjalistyczny w Prabutach Sp. z o.o Prabuty Poland 82-550
    64 Mrukmed. Lekarz Beata Madej-Mruk i Partner. Sp.p Rzeszów Poland 35-021
    65 Specjalistyczny Szpital Onkologiczny NU-MED sp. Z Tomaszów Mazowiecki Poland 97-200
    66 Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu Toruń Poland 87-100
    67 Wojewódzkie Wielospecjalistyczne Centrum Onkologii Łódź Poland 93-513
    68 Institut Català d Oncologia (ICO) - Hospital Germans Trias i Pujol Badalona Barcelona Spain 08916
    69 Hospital Universitario Marqués de Valdecilla Santander Cantabria Spain 39008
    70 Complejo Hospitalario Materno-Insular de Gran Canaria Las Palmas De Gran Canaria Gran Canaria Spain 35016
    71 Complexo Hospitalario Universitario De Vigo (CHUVI) - Hospital Xeral Vigo Pontevedra Spain 36312
    72 Hospital Teresa Herrera C.H.U.A. A Coruña Spain 15009
    73 Hospital HM Nou Delfos Barcelona Spain 08023
    74 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    75 Hospital Universitario Reina Sofía Córdoba Spain 14004
    76 Hospital Universitario Lucus Augusti Lugo Spain 27003
    77 Hospital Universitario La Paz Madrid Spain 28006
    78 Hospital General Universitario Gregorio Marañón Madrid Spain 28007
    79 Clínica Universidad de Navarra Madrid Spain 28027
    80 MD Anderson Cancer Center Madrid Spain 28033
    81 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    82 Hospital Clínico San Carlos Madrid Spain 28040
    83 Hospital Universitario Fundación Jimenez Díaz Madrid Spain 28040
    84 Hospital Universitario 12 de Octubre Madrid Spain 28041
    85 Hospital Universitario HM Sanchinarro Madrid Spain 28050
    86 Hospital Regional Universitario Málaga Hospital Civil Málaga Spain 29010
    87 Hospital Universitario Virgen del Rocío Sevilla Spain 41013
    88 Hospital Universitari i Politècnic La Fe Valencia Spain 46026
    89 Hospital Clínico Universitario de Valladolid Valladolid Spain 47003
    90 Hospital Clínico Universitario Lozano Bleza Zaragoza Spain 50009
    91 Belfast Health and Social Care Trust Belfast United Kingdom BT9 7AB
    92 The Princess Alexandra Hospital Harlow United Kingdom CM20 1QX
    93 University Hospitals of Leicester NHS Trust Leicester United Kingdom LE1 5WW
    94 Guys and St Thomas NHS Foundation Trust London United Kingdom SE1 9RT
    95 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • PharmaMar


    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    PharmaMar Identifier:
    Other Study ID Numbers:
    • PM1183-C-008-21
    First Posted:
    Dec 10, 2021
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by PharmaMar
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022