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)
Relapsed Small Cell Lung Cancer
About this trial
This is an interventional treatment trial for Relapsed Small Cell Lung Cancer focused on measuring Relapsed Small Cell Lung Cancer, PharmaMar, Lurbinectedin, Irinotecan, Topotecan
Eligibility Criteria
Inclusion Criteria:
- Voluntary written informed consent of the patient obtained before any study-specific procedure
- Age≥18 years
- Histologically or cytologically confirmed diagnosis of SCLC.
- 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)
- 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)
- 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
- Eastern Cooperative Oncology Group (ECOG) PS ≤ 2
Adequate hematological, renal, metabolic and hepatic function:
- 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.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
- Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN.
- Albumin ≥ 3.0 g/dL.
- Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
- 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.
- Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
- 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:
- Platinum-naïve patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
- Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
- Active or untreated CNS metastases and/or carcinomatous meningitis.
- 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.
Concomitant diseases/conditions:
- History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
- Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
- Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
- Known Gilbert's disease.
- Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.
- 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.
- 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.
- 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.
- Limitation of the patient's ability to comply with the treatment or to follow the protocol.
- Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
- Known human immunodeficiency virus (HIV) infection.
- Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
- Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
- Active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
- RT in more than 35% of the bone marrow.
- History of previous bone marrow and/or stem cell transplantation and allogenic transplant.
- 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.
- Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
- History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
- Women who are pregnant or breast feeding and fertile patients (men and women) who are not able to use an effective method of contraception
Sites / Locations
- Ironwood Cancer & Research CentersRecruiting
- Genesis Cancer and BloodRecruiting
- Florida Cancer Specialists
- Florida Cancer Specialists
- Florida Cancer Specialists
- Duly Health and CareRecruiting
- Norton Cancer Institue, DowntownRecruiting
- Dana-Farber Cancer InstituteRecruiting
- Oncology Hematology West, PC (Grand Island)Recruiting
- Oncology Hematology West, PC dba Nebraska Cancer SpecialistsRecruiting
- FirstHealth Outpatient Cancer CenterRecruiting
- Utah Cancer SpecialistsRecruiting
- MultiCare Regional Cancer Center - TacomaRecruiting
- Froedtert Hospital/Medical College of WisconsinRecruiting
- The Chris Obrien LifehouseRecruiting
- BRICC - Ballarat Health ServicesRecruiting
- Box Hill Hospital Eastern Health Clinical SchoolRecruiting
- Northern Beaches HospitalRecruiting
- Gosford Hospital GH - Central Coast Cancer CentreRecruiting
- Austin Hospital- Medical Oncology UnitRecruiting
- St John of God Murdoch HospitalRecruiting
- Southern Medical Day Care CentreRecruiting
- University Hospital SalzburgRecruiting
- Medizinische Universitaet Wien
- Antwerp University HospitalRecruiting
- Algemeen Ziekenhuis AZ Klina - BorstkliniekRecruiting
- Grand Hopital de Charleroi GHdC - Hopital Saint JosephRecruiting
- Centre Hospitalier Chretien CHC - MontLegiaRecruiting
- CHR de la CitadelleRecruiting
- CHU LiegeRecruiting
- Az Sint Maarten MechelenRecruiting
- Centre Hospitalier Universitaire (CHU) Ambroise PareRecruiting
- Oncocentro-Centro de Oncologia do ParanaRecruiting
- UPCO - Hospital de Clinicas de Porto Alegre
- Nucleo de Oncologia da Bahia - NOBRecruiting
- Fundacao Pio XII - Hospital de Cancer de Barretos - Hospital de AmorRecruiting
- ONCOSITE - Centro de Pesquisa Clinica em Oncologia LtdaRecruiting
- Irmandade daSanta Casa de Misericordia de Porto AlegreRecruiting
- Hospital Sao Lucas da PUCRSRecruiting
- Instituto Nacional de Cancer - Ministrio da Sade
- Multiprofile Hospital for Active Treatment - Uni Hospital OOD Department of Medical OncologyRecruiting
- Complex Oncology Center - Plovdiv EOOD, First Department of Medical Oncology and Oncological Diseases in GastroenterologyRecruiting
- Specialized hospital for active treatment of oncological diseasesRecruiting
- Multiprofile Hospital for Active Treatment Serdika EOOD Second Department of Medical OncologyRecruiting
- McGill University Health Centre (MUHC)Recruiting
- University Health Network - Princess Margaret Hospital
- SIM-CRRC
- Clinical Research Chile SpA
- Centro de Estudios Clínicos SAGA
- Clinica Alemana de Santiago
- Clínica Santa María
- Fundación Arturo López Pérez
- Hospital Clinico Universidad de Chile
- Aalborg University HospitalRecruiting
- Sjællands UniversitetshospitalRecruiting
- Sønderborg SygehusRecruiting
- Vejle HospitalRecruiting
- Hopital Jean MinjozRecruiting
- AssAP-HP - Hopital Ambroise-PareRecruiting
- Hopital Morvan CHU de BrestRecruiting
- Centre François BaclesseRecruiting
- CHU de Caen - Hopital Cote de NacreRecruiting
- Centre Hospitalier Intercommunal de Creteil (CHIC)Recruiting
- Centre Hospitalier Universitaire CHU De LimogesRecruiting
- CHU de NantesRecruiting
- Bichat-Claude Bernard HospitalRecruiting
- CHU Reims - Hpital Maison BlancheRecruiting
- Hopital Civil / Nouvel Hopital CivilRecruiting
- Hospital FochRecruiting
- Gustave RoussyRecruiting
- High Technology Hospital MedcenterRecruiting
- Todua ClinicRecruiting
- New HospitalsRecruiting
- Institute Of Clinical OncologyRecruiting
- JSC Evex Hospitals "Caraps Medline"Recruiting
- LTD Cancer Research CentreRecruiting
- LungenClinic GrosshansdorfRecruiting
- Zentralklinik Bad Berka GmbH
- Evangelische Lungenklinik Berlin
- Charite - Universitaetsmedizin Berlin
- Klinikum Bremen Ost
- Helios St. Johannes Klinikum
- Klinikum Esslingen GmbHRecruiting
- Universittsklinikum Freiburg
- Asklepios Fachklinik München-GautingRecruiting
- Krankenhaus Martha-Maria Halle gGmbHRecruiting
- Universitaetsklinikum Halle SaaleRecruiting
- Thoraxclinic Heidelberg GmbHRecruiting
- Vincentius-Diakonissen-Kliniken gAG KarlsruheRecruiting
- Klinikum Kassel - Medizinische Klinik IVRecruiting
- Klinik Loewenstein gGmbH
- Universitaetsmedizin MannheimRecruiting
- Staedtisches Klinikum München - Bogenhausen
- Sana Klinikum Offenbach
- Debreceni Egyetem - Klinikai KozpontRecruiting
- Veszprem Megyei Tudogyogyintezet FarkasgyepuRecruiting
- Bacs-Kiskun County HospitalRecruiting
- Hetenyi G Korhaz, Onkologiai KozpontRecruiting
- Pulmonology Hospital TorokbalintRecruiting
- Rambam Health Care Campu
- Shaare Zedek Medical Center
- Rabin Medical Center
- The Chaim Sheba Medical Center
- Tel Aviv Sourasky Medical Center
- A.O. SS. Antonio e Biagio e Cesare Arrigo di AlessandriaRecruiting
- Azienda Ospedaliero Universitaria delle MarcheRecruiting
- IRCCS Centro di Riferimento OncologicoRecruiting
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi Oncologia medicaRecruiting
- Azienda Ospedaliera Univ. Policlinico G Rodolico San Marco
- A.O. Santa Croce e Carle, Ospedale CarleRecruiting
- AOU CareggiRecruiting
- ASL 3 Genovese Oncologia Medica Villa ScassiRecruiting
- IRCCS Istituto Clinico Humanitas - Cancer CenterRecruiting
- Universita degli Studi della Campania Luigi Vanvitelli
- Ospedale Maggiore di NovaraRecruiting
- Azienda Ospedaliero-Universitaria San Luigi GonzagaRecruiting
- Oncologia Medica II Istituto Oncologico Veneto IRCCSRecruiting
- Azienda USL di PiacenzaRecruiting
- Irccs-CrobRecruiting
- Fondazione Policlinico Universitario Campus Bio-MedicoRecruiting
- IFO Regina ElenaRecruiting
- Azienda Ospedaliera Univ. Senese Policlinico Le Scotte
- ASST Valtellina e Alto Lario Ospedale di SondrioRecruiting
- ASST Sette LaghiRecruiting
- Chungbuk National University HospitalRecruiting
- CHA Bundang Medical Center, CHA University
- The Catholic University of Korea, St.Vincents Hospital
- Gachon University Gil Medical Center
- Inha University HospitalRecruiting
- Kangbuk Samsung HospitalRecruiting
- Asan Medical Center
- The Catholic University of Korea, Seoul St. Mary's Hospital
- Seoul Metropolitan Government-Seoul National University Boramae Medical Center
- II Klinika Chorob Pluc i Gruzlicy
- Szpitale Pomorskie Sp. z o.o., Oddzial Onkologii KRecruiting
- Specjalistyczna Praktyka Lekarska Slawomir MandziukaRecruiting
- Szpital Specjalistyczny w Prabutach Sp. z o.oRecruiting
- Mrukmed. Lekarz Beata Madej-Mruk i Partner. Sp.pRecruiting
- Specjalistyczny Szpital Onkologiczny NU-MED sp. Z
- Wojewódzkie Wielospecjalistyczne Centrum OnkologiiRecruiting
- Sc Oncopremium Team SrlRecruiting
- Medisprof srlRecruiting
- Oncolab SRLRecruiting
- Centrul de Oncologie Sfantu NectarieRecruiting
- Ovidius Clinical Hospital
- Oncocenter Oncologie clinica S.R.LRecruiting
- Institut Català d Oncologia (ICO) - Hospital Germans Trias i PujolRecruiting
- Institut Catala d'Oncologia (ICO) - Hospital Duran i ReynalsRecruiting
- Hospital Universitario Marqués de ValdecillaRecruiting
- Complejo Hospitalario Materno-Insular de Gran CanariaRecruiting
- Clínica Universidad de NavarraRecruiting
- Complexo Hospitalario Universitario De Vigo (CHUVI) - Hospital XeralRecruiting
- Hospital Teresa Herrera C.H.U.A.Recruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital Universitario Reina SofíaRecruiting
- Hospital Universitario Lucus AugustiRecruiting
- Hospital Universitario La PazRecruiting
- Hospital General Universitario Gregorio MarañónRecruiting
- Clínica Universidad de NavarraRecruiting
- MD Anderson Cancer CenterRecruiting
- Hospital Universitario Ramón y CajalRecruiting
- Hospital Clínico San CarlosRecruiting
- Hospital Universitario Fundación Jimenez DíazRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital Universitario HM SanchinarroRecruiting
- Hospital Regional Universitario Málaga Hospital CivilRecruiting
- Hospital Universitario Virgen del RocíoRecruiting
- Hospital Universitari i Politècnic La FeRecruiting
- Hospital Clínico Universitario de ValladolidRecruiting
- Hospital Clínico Universitario Lozano BlezaRecruiting
- University Hospital Basel
- Istituto Oncologico della Svizzera Italiana
- Spital Thurgau - Kantonspital Frauenfeld
- Centre Hospitalier Universitaire VaudoisRecruiting
- Kantonsspital Baselland
- Spital Thurgau - Kantonsspital MuensterlingenRecruiting
- HFR Freiburg Kantonsspital
- Medicalpark Seyhan Hospital
- Liv Hospital Ankara
- Bagcilar Medipol Mega University Hospital
- Goztepe Prof. Dr. Suleyman Yalcin City Hospital
- Kocaeli University Hospital
- Belfast Health and Social Care Trust
- The Princess Alexandra HospitalRecruiting
- Guys and St Thomas NHS Foundation TrustRecruiting
- The Christie NHS Foundation TrustRecruiting
- Nottingham University Hospitals NHS TrustRecruiting
- Clatterbridge HospitalRecruiting
- The Royal Wolverhampton NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Lurbinectedin
Lurbinectedin plus Irinotecan
Control arm
Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)
Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): Irinotecan (Day 1 and Day 8) Lurbinectedin (Day 1)
Best Investigator's choice prior to randomization between: Irinotecan on Day 1 q3wk Topotecan on Days 1-5 q3wk