Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer

NCT ID: NCT02566993

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 613 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-30
• Study Completion Date: 2020-02-24

Brief Summary

Phase III randomized clinical trial of lurbinectedin (PM01183)/doxorubicin (DOX) versus cyclophosphamide (CTX), doxorubicin (DOX) and vincristine (VCR) (CAV) or topotecan as treatment in patients with small-cell lung cancer (SCLC) who failed one prior platinum-containing line.

Detailed Description

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of an experimental arm consisting of PM01183/DOX combination followed by PM01183 alone, if applicable vs. best Investigator's choice between CAV or topotecan as a control arm, in SCLC patients who failed one prior platinum-containing line but no more than one prior chemotherapy-containing line.

Conditions

Small-cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm

Lurbinectedin (PM01183) / Doxorubicin

Group Type: EXPERIMENTAL

Lurbinectedin (PM01183)

Intervention Type: DRUG

Doxorubicin (DOX)

Intervention Type: DRUG

Control Arm 1

CAV (Cyclophosphamide (CTX), Doxorubicin (DOX) and Vincristine (VCR))

Group Type: ACTIVE_COMPARATOR

Doxorubicin (DOX)

Intervention Type: DRUG

Cyclophosphamide (CTX)

Intervention Type: DRUG

Vincristine (VCR)

Intervention Type: DRUG

Control Arm 2

Topotecan

Group Type: ACTIVE_COMPARATOR

Topotecan

Intervention Type: DRUG

Interventions

Lurbinectedin (PM01183)

Intervention Type: DRUG

Doxorubicin (DOX)

Intervention Type: DRUG

Cyclophosphamide (CTX)

Intervention Type: DRUG

Vincristine (VCR)

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntary written informed consent

2. Adult patients ≥ 18 years

3. Histologically or cytologically confirmed diagnosis of limited or extensive stage SCLC which failed one prior platinum-containing regimen and with a chemotherapy-free interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence of progressive disease) ≥ 30 days. Small-cell carcinoma of unknown primary site with or without neuroendocrine features confirmed in histology test(s) performed on metastatic lesion(s) are eligible, if Ki-67/MIB-1 is expressed in >50% of tumor cells.

4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2.

5. Adequate hematological, renal, metabolic and hepatic function within 7-10 days prior to randomization

6. At least three weeks since last prior anticancer treatment and adequate recovery from prior treatment toxicity

7. Prior radiotherapy (RT): At least four weeks since completion of whole-brain irradiation, at least two weeks since completion of prophylactic cranial irradiation, and to any other site.

8. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six weeks after treatment discontinuation. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product dose.

Exclusion Criteria

1. More than one prior chemotherapy-containing line(re-challenge with the same initial regimen is not allowed)

2. Patients who never received platinum-containing regimen for Small-cell Lung Cancer (SCLC)

3. Prior treatment with PM01183, topotecan or anthracyclines.

4. Limited-stage patients who are candidates for local or regional therapy

5. Impending need for palliative RT or surgery for pathological fractures and/or for medullary compression within four weeks prior to randomization.

6. Symptomatic or progressing or steroid requiring Central Nervous System (CNS) involvement disease at least four weeks prior to randomization

7. Concomitant diseases/conditions:

Angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease, arrhythmia, immunodeficiency (including known HIV seropositive), ongoing or treatment-requiring chronic liver disease, active infection, oxygen requirement within two weeks prior to randomization, diffuse interstitial lung disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic treatment within 12 weeks of randomization.

8. Pregnant or breast feeding women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Alabama Oncology

Birmingham, Alabama, United States

Ironwood Physicians P.C. dba Ironwood Cancer & Research Centers

Chandler, Arizona, United States

St Jude Hospital Yorba Linda dba St Joseph Heritage Healthcare

Fullerton, California, United States

Loma Linda University Medica! Center

Loma Linda, California, United States

Innovative Clinical Research Institute (ICRI)

Whittier, California, United States

Boca Raton Regional Hospital Lynn Cancer Institute

Boca Raton, Florida, United States

Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center

Fort Lauderdale, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, United States

Healthcare Research Network III, LLC

Tinley Park, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Montgomery Cancer Center

Mount Sterling, Kentucky, United States

East Jefferson Hematology-Oncology Metairie Physicians Services, Inc

Metairie, Louisiana, United States

Anne Arundel Medical Center Oncology and Hematology

Annapolis, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

QUEST Research Institute

Royal Oak, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital

Lebanon, New Hampshire, United States

Summit Medical Group, P.A.

Florham Park, New Jersey, United States

FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

Oklahoma Cancer Specialists and Research Institute, LLC

Tulsa, Oklahoma, United States

Associates in Hematology and Oncology, P.C.

Upland, Pennsylvania, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Tyler Hematology-Oncology PA

Tyler, Texas, United States

Medical Oncology Associates PS (dba Summit Cancer Centers)

Spokane, Washington, United States

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Instituto Médico Especializado Alexander Fleming

C.a.b.a., Buenos Aires, Argentina

Centro para la Atención Integral del Paciente Oncológico (CAIPO)

San Miguel de Tucumán, Tucumán Province, Argentina

Instituto Oncológico de Córdoba (IONC)

Córdoba, , Argentina

CORI - Centro Oncológico Riojano Integral

La Rioja, , Argentina

ISIS Centro Especializado de Luce S.A.

Santa Fe, , Argentina

Universitätsklinik für Innere Medizin III der PMU

Salzburg, , Austria

Medizinische Universität Wien / AKH Wien, Universitätsklinik für Innere Medizin I, Abteilung für klinische Onkologie

Vienna, , Austria

AZ Maria Middelares

Ghent, , Belgium

Clinique André Renard

Herstal, , Belgium

CHR de la citadelle

Liège, , Belgium

CHU de Liege - Sart Tilman

Liège, , Belgium

CHU Ambroise Paré

Mons, , Belgium

AZ Delta Campus Wilgenstraat

Roeselare, , Belgium

Nucleo de Oncologia da Bahia

Salvador, Estado de Bahia, Brazil

lOP- Instituto de oncologia do paraná

Curitiba, Paraná, Brazil

Coordenação de Pesquisa Clínica / Instituto Nacional de Câncer

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto COl de Pesquisa, Educação e Gestão

Rio de Janeiro, Rio de Janeiro, Brazil

Associação Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, Brazil

lrmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de clínicas de Porto alegre

Pôrto Alegre, Rio Grande do Sul, Brazil

Fundação PlO XII - Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

lnstituto de Ensino e Pesquisa Säo Lucas - IEP Säo Lucas

São Paulo, São Paulo, Brazil

Multiprofile Hospital for Active Treatment - Uni Hospital, Panagyurishte

Panagyurishte, , Bulgaria

Multiprofile Hospital for Active Treatment of Women Health - "Nadezhda", Sofia; Clinic of Medical Oncology

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski", Sofia

Sofia, , Bulgaria

Acibadem City Clinic University Multiprofile Hospital for Active Treatment. EOOD, Sofia; Clinic of Medical Oncology

Sofia, , Bulgaria

Southlake Regional Health Centre - Stronach Regional Cancer Centre

Newmarket, Ontario, Canada

R.S. Mc Laughlin Durham Regional Cancer Centre, Lakeridge Health

Oshawa, Ontario, Canada

Centre intégré de santé et de services sociaux de la Montérégie Centre

Greenfield Park, Quebec, Canada

Montreal Oncology Research Inc.

Montreal, Quebec, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Biron (Clinique René Laennec)

Mount Royal, Quebec, Canada

Vitkovicka nemocnice, a.s., Plicni oddeleni

Ostrava, , Czechia

Krajska zdravotni a.s. Masarykova nemocnice o.z.

Ústí nad Labem, , Czechia

Institut Bergonié

Bordeaux, , France

Centre François Baclesse

Caen, , France

Centre Hospitalier Intercommunal de Créteil

Créteil, , France

Centre Hospitalier Lyon Sud - Service de Pneumologie

Lyon, , France

Hôpital Nord - Service Oncologie Multidisciplinaire et Innovations Thérapeutiques

Marseille, , France

Centre Antoine Lacassagne

Nice, , France

CHU de Rennes Hôpital Pontchaillou

Rennes, , France

Central Clinic of Bad Berka

Bad Berka, , Germany

Vivantes Klinikum am Urban, Hämatologie und Onkologie

Berlin, , Germany

Evangelische Lungenklinik Berlin

Berlin, , Germany

Uniklinik Freiburg, Hämatologie, Onkologie & Stammzellransplantation

Freiburg im Breisgau, , Germany

Asklepios-Fachkliniken München Gauting

Gauting, , Germany

Center for Pneumology and Thoracic Surgery

Gerlingen, , Germany

Thoraxklinik Heidelberg GmbH

Heidelberg, , Germany

Lungenklinik Hemer

Hemer, , Germany

VIDIA Christliche Kliniken Karlsruhe

Karlsruhe, , Germany

Katholisches Klinikum Koblenz-Montabaur, Marienhof Koblenz

Koblenz, , Germany

Onkologische Schwerpunktpraxis Leer-Emden

Leer, , Germany

Klinik Löwenstein gGmbH, Med. Klinik II Onkologie

Löwenstein, , Germany

Uniklinikum Mannheim, TTZ, Medizinische Fakultät Mannheim

Mannheim, , Germany

Johannes Wesling Klinikum Minden, Klinik für Hämatologie, Onkologie und Palliativmedizin

Minden, , Germany

University of Munich LMU, Dpt. of Medicine V

München, , Germany

Städtisches Krankenhaus München Neuperlach

München, , Germany

Klinikum Bogenhausen, Städt. Klinikum München GmbH, Klinik für Pneumologie und Pneumologische Onkologie

München, , Germany

Klinikum Nürnberg Nord - Pneumologische Onkologie

Nuremberg, , Germany

Universitätsklinikum Ulm - Klinik für Innere Medizin II, Pneumologie

Ulm, , Germany

Medizinische Klinik I

Wuppertal, , Germany

University General Hospital of Heraklion - General Hospital "Venizeleio"

Heraklion, Crete, Greece

General Hospital of Chest Diseases of Athens "Sotiria"

Athens, , Greece

General Oncology Hospital of Kifissia "Agioi Anargiroi", 2nd Internal Medicine-Oncology Clinic

Athens, , Greece

General Hospital of Thessaloniki "G. Papanikolaou", Pulmonary Clinic, Aristotle University of Thessaloniki

Thessaloniki, , Greece

Országos Korányi TBC és Pulmonológiai Intézet, 6. Pulmonológia és Bronchologia

Budapest, , Hungary

Országos Korányi TBC és Pulmonológiai lntézet, 14. Pulmonológia

Budapest, , Hungary

Veszprém Megyei Tüdögyógyintézet, 3. Pulmonológiai Osztály

Farkasgyepű, , Hungary

Mátrai Gyógyintézet, Bronchológia

Mátraháza, , Hungary

Miskolci Semmelweis Kórház és Egyetemi Oktatókórház, Pulmonológiai Osztály

Miskolc, , Hungary

Fejér Megyei Szent György Egyetemi Oktató Kórház, I. Pulmonológiai Osztály

Székesfehérvár, , Hungary

Markusovszky Egyetemi Oktatókórház, Pulmonológiai Osztály

Szombathely, , Hungary

Szent Borbála Kórház, Pulmonológiai osztály

Tatabánya, , Hungary

Zala Megyei Kórház, Pulmonologia

Zalaegerszeg, , Hungary

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, Italy

IRCCS CROB (Istituto di Ricovero e Cura a Carattere Scientifico)

Rionero in Vulture, PZ, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, , Italy

Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele" - Presidio G. Rodolico

Catania, , Italy

AOU Maggiore della Carità - SC Oncologia

Novara, , Italy

Istituto Oncologico Veneto

Padua, , Italy

lRCCS-Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Policlinico Universitario Campus Bio-Medico

Roma, , Italy

ASST della Valtellina e dell' Alto Lario P.O. Di Sondrio

Sondrio, , Italy

Ain Wazein Hospital

Ain Wazein, El Chouf, Lebanon

American University of Beirut Medical Center

Beirut, , Lebanon

Hotel Dieu de France

Beirut, , Lebanon

Centre Hospitalier Universitaire Notre Dame de Secours

Byblos, , Lebanon

Hammoud Hospital University Medical Center

Sidon, , Lebanon

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Spaarne Gasthuis

Hoofddorp, , Netherlands

MUMC

Maastricht, , Netherlands

Maxima Medisch Centrum

Veldhoven, , Netherlands

Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie; Oddzial Onkologii Klinicznej im. dr Ewy Pileckiej z pododdzialem

Bialystok, , Poland

Szpitale Pomorskie Sp. z o.o., Oddzial Onkologii Klinicznej, Oddzial Onkologii i Radioterapii

Gdynia, , Poland

Mazowieckie Centrum Leczenia Chorób Pluc i Gruźlicy Oddzial III Chorób Pluc z Pododdzialem Onkologicznym

Otwock, , Poland

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. K.Marcinkowskiego w Poznaniu, Oddzial Chemioterapii

Poznan, , Poland

Centro Clínico Champalimaud - Fundação Champalimaud

Lisbon, , Portugal

Centro Hospitalar Lisboa Norte, EPE- Hospital Pulido Valente

Lisbon, , Portugal

Centro Hospitalar do Porto, EPE - Hospital de Santo António

Porto, , Portugal

Hospital CUF Porto

Porto, , Portugal

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, , Portugal

Centro Hospitalar de São João, EPE

Porto, , Portugal

SC Centrul de Oncologie Sf. Nectarie SRL, Departament Oncologie Medícala

Craiova, Dolj, Romania

Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei"

Constanța, Judet Constanta, Romania

SC Oncolab SRL

Craiova, Judet Dolj, Romania

Spitalul Judetean de Urgenta "Dr. Constantin Opris", Sectia Oncologie Medicala

Baia Mare, Maramureş, Romania

Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca, Departament Oncologie Medicala

Cluj-Napoca, , Romania

Institutul Oncologic "Prof. Dr. lon Chiricuta" Cluj-Napoca, Dcpartamentul Oncologie Medicala

Cluj-Napoca, , Romania

Institutul Oncologic "Prof. Dr. lon Chiricuta" Cluj-Napoca, Sectia Oncologic Medicala

Cluj-Napoca, , Romania

Hospital Universitari Germans Trias i Pujol ICO

Badalona, Barcelona, Spain

Corporació Sanitaria Parc Taulí-Hospital de Sabadell

Sabadell, Barcelona, Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitari Vall d' Hebron

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

MD Anderson Cancer Center Madrid

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Complejo hospitalario regional virgen rocío

Seville, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Hospital Universitario La Fe de Valencia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

The Christie NHS Fundation Trust

Manchester, Greater Manchester, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Bristol Cancer Institute, UHB NHS Foundation Trust

Bristol, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Sarah Cannon Research Institute UK

London, , United Kingdom

Worcestershire Acute Hospitals NHS Trust

Worcester, , United Kingdom

Countries

United States; Argentina; Austria; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Greece; Hungary; Italy; Lebanon; Netherlands; Poland; Portugal; Romania; Spain; United Kingdom

References

Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohe C, Farago AF, Lopez-Vilarino JA, Cullell-Young M, Nieto A, Vasco N, Gomez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sanchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Domine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. doi: 10.1016/S2213-2600(22)00309-5. Epub 2022 Oct 14.

Reference Type: DERIVED

PMID: 36252599 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PM1183-C-003-14

Identifier Type: -

Identifier Source: org_study_id