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Dinutuximab and Irinotecan Versus Irinotecan to Treat Subjects With Relapsed or Refractory Small Cell Lung Cancer

Sponsor
United Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03098030
Collaborator
(none)
483
Enrollment
226
Locations
4
Arms
33.8
Actual Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a 2-part, multicenter, open-label, randomized study of dinutuximab and irinotecan versus irinotecan alone in subjects with relapsed or refractory small cell lung cancer (SCLC). Part 1 of the study involves intrasubject dose escalation to evaluate the safety and tolerability of dinutuximab in combination with irinotecan. Part 2 of the study is designed to determine whether dinutuximab plus irinotecan prolongs overall survival (OS) compared with irinotecan alone. Subjects in Part 2 will be randomized in a 2:2:1 fashion to 1 of 3 treatment groups: (A) irinotecan; (B) dinutuximab plus irinotecan; or (C) topotecan. Randomization will be stratified by duration of response to prior platinum therapy (relapse-free period <3 months or ≥3 months).

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
483 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Two-part, Open-label, Randomized, Phase 2/3 Study of Dinutuximab and Irinotecan Versus Irinotecan for Second Line Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer
Actual Study Start Date :
Jun 1, 2017
Actual Primary Completion Date :
Jan 27, 2020
Actual Study Completion Date :
Mar 26, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Dinutuximab + Irinotecan

Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.

Biological: Dinutuximab
Dinutuximab injection, for intravenous (IV) use
Other Names:
  • Unituxin®
  • ch14.18

    • Drug: Irinotecan
    Irinotecan injection, IV infusion
    Other Names:
  • Camptosar®

    		•
    Active Comparator: Part 2: Irinotecan

    Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle.

    Drug: Irinotecan
    Irinotecan injection, IV infusion
    Other Names:
  • Camptosar®

    		•
    Experimental: Part 2: Dinutuximab + Irinotecan

    Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.

    Biological: Dinutuximab
    Dinutuximab injection, for intravenous (IV) use
    Other Names:
  • Unituxin®
  • ch14.18

    • Drug: Irinotecan
    Irinotecan injection, IV infusion
    Other Names:
  • Camptosar®

    		•
    Active Comparator: Part 2: Topotecan

    Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle.

    Drug: Topotecan
    Topotecan for injection
    Other Names:
  • Hycamtin®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 2.5 years]

      OS will be derived as: (date of death - date of randomization) + 1. Subjects who are alive or permanently lost to follow-up at the cut-off date for the analysis will be censored at the last date the subject was known to be alive.

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) [Up to approximately 2.5 years]

      PFS will be defined as the time from the date of randomization to the date of first documentation of tumor progression or death from any cause, whichever occurs first.

    2. Objective Response Rate (ORR) [Up to approximately 2.5 years]

      The ORR is the percentage of subjects with best overall response of either complete response (CR) or partial response (PR); ORR = CR + PR. Per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters as confirmed by CT or MRI.

    3. Clinical Benefit Rate (CBR) [Up to approximately 2.5 years]

      The CBR is defined as the percentage of subjects with either a CR, PR, or stable disease (SD), relative to the number of subjects in the treatment group. Per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, CR was defined as the disappearance of all target lesions; PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study, as confirmed by CT or MRI .

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Have histologically or cytologically confirmed SCLC (undifferentiated small-cell carcinoma arising in or consistent with lung cancer origin).

    2. Documented relapse or disease progression during or after first-line platinum-based therapy (subjects refractory to initial platinum-based therapy are eligible).

    3. Have no curative therapy available.

    4. Have a life expectancy of at least 12 weeks.

    5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    6. Have adequate bone marrow and hepatic function.

    7. Have calculated creatinine clearance (CrCL) ≥30 mL/minute or serum creatinine ≤1.5 times below the upper limit of normal.

    8. Women of reproductive potential must not be pregnant or breastfeeding and have a negative urine or serum pregnancy test obtained within 7 days prior to the first dose of study treatment.

    9. Subjects must agree to consistently use 2 forms of highly effective contraception/birth control between signing of the informed consent and 60 days after the last study drug administration.

    Exclusion Criteria:

    1. Candidate for re-treatment with original platinum-based regimen as second-line therapy.

    2. Prior treatment with irinotecan, topotecan, or dinutuximab.

    3. Have active brain metastases. Subjects with brain metastases are allowed if they completed definitive brain therapy, are asymptomatic and radiologically stable, and if they are not currently receiving corticosteroids or radiation.

    4. Have mixed small cell and non-small cell histologic features.

    5. Have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis [carcinoma in situ]) or any previous cancer curatively treated <3 years ago.

    6. Have a history or current evidence of uncontrolled cardiovascular disease.

    7. Have not recovered from prior surgery, significant trauma, systemic anticancer therapy, radiation therapy or investigational therapy to Grade 1 or better toxicity prior to enrollment (Part 1) or randomization (Part 2).

    8. Have had organ allograft or hematopoietic transplantation.

    9. Known to be human immunodeficiency virus (HIV) positive.

    10. Have an active infection requiring treatment or one that is clinically serious in the Investigator's opinion.

    11. Have received a live vaccine within 6 months of enrollment (Part 1) or randomization (Part 2).

    12. Exposure to strong CYP3A4 and/or UGT1A1 inhibitors and strong CYP3A4 inducers within 14 days of enrollment (Part 1) or randomization (Part 2).

    13. Have any clinical condition that is considered unstable or might jeopardize the safety of the subject and/or influence the subject's compliance in the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alaska Clinical Research Center Anchorage Alaska United States 99503
    2 Cancer Treatment Centers of America - Western Regional Medical Center Goodyear Arizona United States 85338
    3 Innovative Clinical Research Institute Tucson Arizona United States 85745
    4 Genesis Cancer Center Hot Springs Arkansas United States 71913
    5 USC Norris Comprehensive Cancer Center Los Angeles California United States 90033
    6 VA Palo Alto Health Care System Palo Alto California United States 94304
    7 Olive View - UCLA Sylmar California United States 91342
    8 Innovative Clinical Research Institute Whittier California United States 90603
    9 Hartford Hospital Hartford Connecticut United States 06062
    10 Eastern Connecticut Hematology and Oncology Assoc Norwich Connecticut United States 06360
    11 Alpha Oncology Research LLC DeBary Florida United States 32713
    12 21st Century Oncology Jacksonville Florida United States 32204
    13 Comprehensive Hematology Oncology Saint Petersburg Florida United States 33709
    14 Winship Cancer Institute, Emory University Atlanta Georgia United States 30322
    15 Northwest Georgia Oncology Centers, P.C. Marietta Georgia United States 30060
    16 Baptist Health Floyd Cancer Center New Albany Indiana United States 47150
    17 Physicians' Clinic of Iowa Hematology and Oncology Cedar Rapids Iowa United States 52403
    18 Kentucky Cancer Clinic Hazard Kentucky United States 41701
    19 University of Kentucky Lexington Kentucky United States 40506
    20 21st Century Oncology Louisville Kentucky United States 40215
    21 Cox Health Medical Springfield Missouri United States 65807
    22 Billings Clinic Cancer Center Billings Montana United States 59101
    23 St. Vincent Frontier Cancer Center Billings Montana United States 59102
    24 The University of New Mexico Comprehensive Cancer Center Albuquerque New Mexico United States 87131
    25 UH Cleveland Medical Center Cleveland Ohio United States 44106
    26 Cancer Treatment Centers of America at Southwestern RMC Tulsa Oklahoma United States 74133
    27 Kaiser Permanente Northwest Center for Health Research CRSS Portland Oregon United States 97227
    28 Fox Chase Cancer Center Office of Clinical Research Philadelphia Pennsylvania United States 19111
    29 Cancer Treatment Centers of America at Eastern Regional Medical Center Philadelphia Pennsylvania United States 19124
    30 Charleston Oncology Charleston South Carolina United States 29414
    31 Spartanburg Medical Center/Gibbs Cancer Center and Research Institute Spartanburg South Carolina United States 29303
    32 Prairie Lakes Health Care Watertown South Dakota United States 57201
    33 Center for Biomedical Research Knoxville Tennessee United States 37909
    34 Texas Health Physicians Group Arlington Texas United States 76012
    35 Plano Cancer Institute Plano Texas United States 75093
    36 The University of Texas Health Science Center at Tyler, Office of Clinical Studies Tyler Texas United States 75701
    37 Vista Oncology (Shelton office) Shelton Washington United States 98584
    38 United Hospital Center Bridgeport West Virginia United States 26330
    39 Camden Clark Medical Center / Regional Cancer Center Parkersburg West Virginia United States 26101
    40 University of Wisoncsin - Carbone Cancer Ctr Madison Wisconsin United States 53792
    41 Mid North Coast Cancer Institute Coff Habour Health Campus Coffs Harbour New South Wales Australia NSW 2450
    42 Mater Misericordiae Limited and Mater Medical Research Institute Limited South Brisbane Queensland Australia QLD 4101
    43 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    44 Ballarat Health Services Ballarat Victoria Australia 3350
    45 Medical Oncology Department, Specialized Hospital for Active Treatment of Oncology Sveti Mina EOOD - Blagoevgrad Blagoevgrad Bulgaria 2700
    46 Department of Medical Oncology, Complex Oncology Center - Burgas EOOD, Burgas Burgas Bulgaria 8000
    47 Medical Oncology Department, Multiprofile Hospital for Active Treatment - Dobrich AD, Dobrich Dobrich Bulgaria 9300
    48 Medical Oncology Department, Multiprofile Hospital for Active Treatment - Dr. Tota Venkova AD, Gabrovo Gabrovo Bulgaria 5300
    49 Medical Oncology Department, Multiprofile Hospital for Active Treatment - Uni Hospital OOD, Panagiurishte Panagyurishte Bulgaria 4500
    50 Clinic of Oncology, UMHAT Dr. Georgi Stranski - Pleven Pleven Bulgaria 5800
    51 Clinic of Oncology, UMHAT Pulmed Plovdiv Bulgaria 4001
    52 First Department of Medical Oncology, Gastroenterology and Pulmology, Complex Oncology Center - Plovdiv EOOD Plovdiv Bulgaria 4004
    53 First Department for Medical Oncology, Multiprofile Hospital for Active Treatement Serdika EOOD, Sofia Sofia Bulgaria 1303
    54 Medical Oncology Clinic, Multiprofile Hospital for Active Treatment (MHAT) for Female's Health - Nadezhda OOD, Sofia Sofia Bulgaria 1330
    55 Medical Oncology Department, University Multiprofile Hospital for Active Treatment Sv. Ivan Rilski EAD, Sofia Sofia Bulgaria 1431
    56 Clinic for Chemotherapy, Specialized Hospital for Active Treatment in Oncology EAD, Sofia Sofia Bulgaria 1756
    57 Clinic of Oncology, UMHAT SofiaMed Sofia Bulgaria 1797
    58 Clinic of Oncology, MHAT Sveta Marina Varna Bulgaria 9010
    59 Cross Cancer Institute - Clinical Trials Unit Edmonton Alberta Canada T6G 1Z2
    60 Horizon Health Network - The Moncton Hosoital Moncton New Brunswick Canada E1C 6Z8
    61 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    62 Windsor Regional Hospital Cancer Program Windsor Ontario Canada N8W 2X3
    63 McGill University Health Center Montréal Quebec Canada H4A 3J1
    64 L'Institut Universitaire de Cardiologie et de pneumologie de Quebec Québec Quebec Canada G1V 4G5
    65 Hopital Nord Marseille Alpes-Côte d'Azur France 13915
    66 Institut Regional du Cancer de Montpellier Montpellier Occitanie France 34298
    67 Institut de Cancérologie de l'Ouest - Centre Paul Papin Angers Pays De La Loire France 49055
    68 Clinique Victor Hugo Le Mans Pays De La Loire France 72000
    69 URCOT : Unité de Recherche Commune en Oncologie Thoracique Service de pneumologie de l'hôpital de la Croix-Rousse Bron Rhône-Alpes France 69677
    70 URCOT : Unité de Recherche Commune en Oncologie Thoracique Service de pneumologie de l'hôpital de la Croix-Rousse Lyon Rhône-Alpes France 69004
    71 Service de Pneumologie aiguë et Cancérologie Thoracique Centre hospitalier Lyon-Sud Pierre Bénite Rhône-Alpes France 69945
    72 CHU Brest Brest France 29609
    73 Centre François Baclesse Caen France 14000
    74 CHI Créteil Créteil France 94010
    75 Institut Paoli-Calmettes, Service Dòncologie Médicale Marseille France 13009
    76 Institut de Cancérologie de l'Ouest - Centre René Gauducheau Saint-Herblain France 44805
    77 Centre Paul Strauss Strasbourg France 67065
    78 Nouvel Hôpital Civil de Strasbourg Strasbourg France 67091
    79 LTD High Technology Hospital Medcenter Batumi Georgia 6000
    80 LTD ''Accad. F. Todua Medical Center-Research Institute of Clinical Medicine'' Tbilisi Georgia 0112
    81 High Technology Medical Center, University Clinic Tbilisi Georgia 0144
    82 Institute of Clinical Oncology Tbilisi Georgia 0159
    83 Multiprofile Clinic Consillium Medulla Tbilisi Georgia 0186
    84 Princess Margaret Hospital Kowloon Hong Kong
    85 Queen Elizabeth Hospital Kowloon Hong Kong
    86 Queen Mary Hospital Pokfulam Hong Kong
    87 Hetenyi Geza Hospital Szolnok Jasz-Nagykun-Szolnok Hungary 5004
    88 Koranyi National Institute of Pulmonology - Horváth Budapest Hungary 1121
    89 Koranyi National Institute of TBC and Pulmonology Budapest Hungary 1121
    90 Korányi National Institute Budapest Hungary 1121
    91 Semmelweis Egyetem AOK Pulmonologiai Klinika Budapest Hungary 1125
    92 Veszprém Megyei Tüdőgyógyintézet Farkasgyepű Hungary 8582
    93 Matrai Gyogyintezet Matrahaza Hungary 3233
    94 Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház, Semmelweis Tagkórház, Tüdőgyógyászati Osztály Miskolc Hungary 3529
    95 Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza Tatabanya Hungary 2800
    96 Tudogyogyintezet Torokbalint Torokbalint Hungary 2045
    97 Zala Megyei Szent Rafael Korhaz Zalaegerszeg Hungary 8900
    98 Sri Venkateshwara Hospitals Bangalore Karnataka India 560076
    99 KLES Dr Prabhakar Kore Hospital & MRC Nehru Nagar Karnataka India 590010
    100 Jaslok Hospital & Research Center Mumbai Maharashtra India 400026
    101 Deenanath Mangeshkar Hospital Pune Maharashtra India 411001
    102 Grant Medical Foundation Ruby Hall Clinic Pune Maharashtra India 411001
    103 Birla Cancer Centre, SMS Hospital Jaipur Rajasthan India 302004
    104 Healthcare Global (HCG) Towers Bangalore India 560020
    105 Bhagawan Mahaveer Cancer Hospital Jaipur India 302017
    106 Dipartimento di Oncologia, ARNAS Garibaldi Catania Italy 95122
    107 Istituto Nazionale dei Tumori Milan Italy 20123
    108 Istituto Europeo di Oncologia (IEO), Milano Milan Italy
    109 Ospedale Santa Maria della Misericordia, Perugia Perugia Italy
    110 Radiation Oncology, Campus Bio-Medico University Rome Italy I-00128
    111 Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena Siena Italy I-53100
    112 A.O.U. San Luigi Gonzaga, Orbassano (Torino) Torino Italy
    113 Kosin University Gospel Hospital Busan Korea, Republic of 49267
    114 Chungbuk National University Hospital Chungcheongbuk-do Korea, Republic of 28644
    115 Kyungpook National University Medical Center Daegu Korea, Republic of 41404
    116 Kyungpook University Chilgok Hospital Daegu Korea, Republic of 41404
    117 Keimyung University Dongsan Medical Centre Daegu Korea, Republic of 42601
    118 Chungnam National University Hospital Daejeon Korea, Republic of 35015
    119 CHA Bundang Medical Center Gyeonggi-do Korea, Republic of 13496
    120 Seoul National University Bundang Hospital Gyeonggi-do Korea, Republic of 13620
    121 Pusan National University Yangsan Hospital Gyeongsangnam-do Korea, Republic of 50612
    122 Inha University Hospital Incheon Korea, Republic of 22332
    123 Chonnam National University Hwasun Hospital Jeonnam Korea, Republic of 58128
    124 Gachon Universtiy Gil Medical Center Namdong Korea, Republic of
    125 Korea University Anam Hospital Seoul Korea, Republic of 02841
    126 Seoul National University Boramae Medical Center Seoul Korea, Republic of 07061
    127 Ulsan University Hospital Ulsan Korea, Republic of 44033
    128 Wonju Severance Christian Hospital Wonju-Si, Gangwon-do Korea, Republic of 26426
    129 Hospital of Lithuanian University of Health Sciences (LSMU) Kauno Klinikos Kaunas Lithuania 50161
    130 National Cancer Institute Vilnius Lithuania 08660
    131 Vilnius University Hospital Santaros Klinikos Vilnius Lithuania 08661
    132 Hospital Kuala Lumpur Kuala Lumpur Malaysia 50586
    133 Department of Medicine, Faculty of Medicine Kuala Lumpur Malaysia
    134 Hospital Umum Sarawak Kuching Malaysia 93586
    135 National Cancer Institute Putrajaya Malaysia 62250
    136 Cebu Doctors University Hospital Cebu City Philippines 6000
    137 Davao Doctors Hospital Davao City Philippines 8000
    138 Manila Doctors Hospital Manila Philippines 1000
    139 St. Luke's Medical Center - Quezon City Quezon City Philippines 1102
    140 St. Luke's Medical Centre Quezon City Philippines 1102
    141 Szpital Specjalistyczny w Prabutach Sp. z o.o Prabuty Pomeranian Voivodeship Poland 82-550
    142 Samodzielny Publiczny Zespół Gruźlicy i Chorób Płuc w Olsztynie Olsztyn Warminsko-Mazurskie Poland 10-357
    143 Samodzielny Specjalistyczny ZespółZakładów Opieki Zdrowotnej im. dr. Teodora Dunina Mrozy Poland 05-320
    144 Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy Otwock Poland 05-400
    145 Szpital Chorób Płuc im Św. Józefa w Pilchowicach Pilchowice Poland 44-145
    146 Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandów Poznań Poland 60-569
    147 Centrum Onkologii-Instytut im. Sklodowskiej-Curie Warszawa Poland 02-781
    148 Wojskowy Instytut Medyczny Warszawa Poland 04-141
    149 Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna Łódź Łódź Voivodeship Poland 90-242
    150 Oncopremium Team LTD Baia-Mare Romania 430291
    151 Institute of Oncology Prof. Dr. I.Chiricuta Cluj-Napoca Cluj-Napoca Romania 400015
    152 Medisprof LTD Cluj-Napoca Romania 400058
    153 SC Oncolab LTD Craiova Romania 200385
    154 SC Oncology Center Sf. Nectarie LTD Craiova Romania
    155 Emergency County Hospital Satu-Mare, Medical Oncology Clinic Satu-Mare Romania 440055
    156 Emergency Hospital ,Sf. Ioan cel Nou' Suceava Romania 720224
    157 Oncocenter Oncology Clinic LTD Timisoara Romania 300166
    158 State Budgetary Healthcare Institution of Arkhangelsk Region Arkhangelsk Clinical Oncology Dispensary Arkhangelsk Russian Federation 163045
    159 State Budgetary Healthcare Institution of Sverdlovsk Region, Sverdlovsk Regional Oncology Dispensary Ekaterinburg Russian Federation 620036
    160 Region Budgetary Healthcare Institution, Kursk Regional Clinical Oncology Dispensary of Healthcare Committee of Kursk Region Kursk Russian Federation 305524
    161 Federal State Budgetary Institution, Natiоnal Medical Research Center of Oncology n.a. N.N. Blokhin of Ministry of Healthcare of the Russian Federation Moscow Russian Federation 115478
    162 State Budgetary Healthcare Institution of Moscow, Moscow City Oncology Hospital #62 of Moscow Healthcare Department Moscow Russian Federation 143423
    163 State Budgetary Healthcare Institution of Arkhangelsk region "Arkhangelsk Clinical Oncology Dispensary" Moscow Russian Federation
    164 State Budgetary Healthcare Institution of Novosibirsk Region, Сity Clinical Hospital #1 Novosibirsk Russian Federation 630047
    165 State Budgetary Healthcare Institution of Novosibirsk Region, Novosibirsk Regional Oncology Dispensary Novosibirsk Russian Federation 630108
    166 Budgetary Healthcare Institution of Omsk Region, Clinical Oncology Dispensary Omsk Russian Federation 644013
    167 State Budgetary Healthcare Institution, Orenburg Regional Clinical Oncology Dispensary Orenburg Russian Federation 460021
    168 Center of Palliative Care-Devita LLC Saint Petersburg Russian Federation 197183
    169 State Budgetary Healthcare Institution, Leningrad Regional Clinical Hospital Saint-Petersburg Russian Federation 194291
    170 BioEq, LLC Saint-Petersburg Russian Federation 197342
    171 Federal State Budgetary Institution, Scientific Research Institute of Oncology n.a. Petrov Saint-Petersburg Russian Federation 197758
    172 State Budgetary Healthcare Institution, Saint-Petersburg Clinical Scientific Practical Center of Specialized Kinds of Medical Care (Oncological) Saint-Petersburg Russian Federation 197758
    173 Saint-Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary Saint-Petersburg Russian Federation 198255
    174 State Budgetary Healthcare Institution, Samara Regional Clinical Oncology Dispensary Samara Russian Federation 443031
    175 State Budgetary Healthcare Institution of Yaroslavl Region, Regional Oncology Hospital Yaroslavl Russian Federation 150054
    176 St. Jacob´s Hospital Bardejov - Department of Clinical Oncology Bardejov Slovakia 08501
    177 Faculty Hospital Zilina Žilina Slovakia 012 07
    178 Hospital General Universitario de Elche Elche Alicante Spain 03203
    179 Hospital Universitario Marqués de Valdecilla Santander Cantabria Spain 39008
    180 CHU A Coruña Coruña Galicia Spain 15006
    181 Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain 28222
    182 Complejo Hospitalario de Navarra Pamplona Navarra Spain 31008
    183 Hospital General de Alicante Alicante Spain 03010
    184 Hospital Quirón Dexeus Barcelona Spain 08028
    185 Hospital Universitari Vall d´Hebron Barcelona Spain 08035
    186 Hospital Universitario Reina Sofia Córdoba Spain 14004
    187 Instituto Catalán de Oncología (ICO) - Josep Trueta Girona Spain 17007
    188 Hospital Universitario Lucus Augusti Lugo Spain 27003
    189 Hospital General Universitário Gregorio Marañón Madrid Spain 28007
    190 Hospital Universitario La Paz Madrid Spain 28046
    191 Hospital Universitario Madrid Norte Sanchinarro Madrid Spain 28050
    192 H. M. Puerta del Sur (H. Móstoles) Madrid Spain 28938
    193 Hospital Regional de Málaga (H. Carlos Haya) Málaga Spain 29006
    194 Complexo Hospitalario Universitario de Ourense (CHUO) Ourense Spain 32005
    195 Hospital Virgen de los Lirios Alcoy Planta Spain 03804
    196 Corporació Sanitària Parc Taulí Sabadell Spain 08208
    197 Hospital Universitario Virgen de Valme Sevilla Spain 41014
    198 Hospital Universitario y Politécnico de La Fe Valencia Spain 46026
    199 Hospital Álvaro Cunqueiro Vigo Spain 36312
    200 Hospital Lozano Blesa Zaragoza Spain 50009
    201 E-Da Hospital Kaohsiung City Taiwan 42445
    202 E-Da Hospital Kaohsiung City Taiwan 82445
    203 Kaohsiung Chang Gung Memorial Hospital Kaohsiung City Taiwan 83301
    204 Chung Shan Medical University Hospital Taichung City Taiwan 402
    205 Chi Mei Hospital, Liouying Tainan City Taiwan 736
    206 Chang-Gung Memorial Hospital, Linkou Taoyuan City Taiwan 33305
    207 King Chulalongkorn Memorial Hospital Bangkok Thailand 10330
    208 National Cancer Institute of Thailand Bangkok Thailand 10400
    209 Siriraj Hopsital Bangkok Thailand 10700
    210 Maharaj Nakorn Chiang Mai Hospital Chiang Mai Thailand 50200
    211 Srinagarind Hospital Khon Kaen Thailand 40002
    212 Naresuan University Hospital Phitsanulok Thailand 65000
    213 Songklanagarind Hospital Songkhla Thailand 90110
    214 Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council," Municipal Institution "Multifield Dnipropetrovsk City Hospital #4" of Dnipropetrovsk Regional Council, Department of Chemotherapy Dnipro Dnipropetrovsk Ukraine 49102
    215 Municipal Nonprofit Institution "Cental Municipal Clinical Hospital" of Uzhgorod City Council, Municipal Oncology Centre Uzhgorod Zakarpattia Ukraine 88000
    216 Regional Communal Nonprofit Enterprise, Municipal Institution Chernivtsi Regional Clinical Oncology Dispensary, Surgery Department, State Higher Educational Establishment of Ukraine, Bukovinian State Medical University, Department of Onc and Radiology Chernivtsi Ukraine 58013
    217 Communal Non-profit Enterprise "Kyiv City Clinical Oncology Center" of Executive body of Kyiv City Council, Kyiv City Clinical Oncology Center by Main Department of Health Protection Kyiv, Hospital of Day Stay for Oncology Patients Kiev Ukraine 03115
    218 Municipal Nonprofit Institution "Odessa Regional Oncology Dispensary" of Odessa Regional Council, Municipal Institution Odesa Regional Oncology Dispensary, Hospital of Day Stay (Unit of Dispensary-Polyclinic Department) Odessa Ukraine 65055
    219 Municipal Nonprofit Institution "Podilsky Regional Oncology Center" of Vinnytsa City Council, Podilsky Regional Oncology Сenter, Department of Chemotherapy Vinnitsya Ukraine 21029
    220 Princess Alexandra Hospital Harlow Essex United Kingdom CM20 1QX
    221 Royal Marsden Hospital Chelsea London United Kingdom SW3 6JJ
    222 St James' Institute of Oncology Leeds United Kingdom LS9 7TF
    223 St Bartholomew's Hospital London United Kingdom EC1A 7BE
    224 Royal Free Hospital London United Kingdom NW3 2QG
    225 Guy's and St Thomas' NHS Foundation Trust London United Kingdom SE1 9RT
    226 Royal Marsden Hospital Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • United Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    United Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03098030
    Other Study ID Numbers:
    • DIV-SCLC-301
    First Posted:
    Mar 31, 2017
    Last Update Posted:
    Dec 9, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by United Therapeutics
    Dinutuximab
    Irinotecan
    Topotecan
    Additional relevant MeSH terms:
    Lung Neoplasms
    Small Cell Lung Carcinoma
    Irinotecan
    Topotecan
    Dinutuximab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    Period Title: Overall Study
    STARTED 12 187 190 94
    COMPLETED 2 24 24 9
    NOT COMPLETED 10 163 166 85

    Baseline Characteristics

    Arm/Group Title Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan Total
    Arm/Group Description Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection Total of all reporting groups
    Overall Participants 12 187 190 94 483
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    67.9
    (8.8)
    61.3
    (8.7)
    61.5
    (9.0)
    62.5
    (8.4)
    61.6
    (8.7)
    Sex: Female, Male (Count of Participants)
    Female
    4
    33.3%
    45
    24.1%
    43
    22.6%
    26
    27.7%
    118
    24.4%
    Male
    8
    66.7%
    142
    75.9%
    147
    77.4%
    68
    72.3%
    365
    75.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    5
    2.7%
    2
    1.1%
    4
    4.3%
    11
    2.3%
    Not Hispanic or Latino
    4
    33.3%
    137
    73.3%
    142
    74.7%
    72
    76.6%
    355
    73.5%
    Unknown or Not Reported
    8
    66.7%
    45
    24.1%
    46
    24.2%
    18
    19.1%
    117
    24.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    28
    15%
    34
    17.9%
    18
    19.1%
    80
    16.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    0.5%
    2
    1.1%
    3
    3.2%
    6
    1.2%
    White
    4
    33.3%
    113
    60.4%
    106
    55.8%
    54
    57.4%
    277
    57.3%
    More than one race
    0
    0%
    0
    0%
    1
    0.5%
    0
    0%
    1
    0.2%
    Unknown or Not Reported
    8
    66.7%
    45
    24.1%
    47
    24.7%
    19
    20.2%
    119
    24.6%
    Region of Enrollment (Count of Participants)
    Southeast Asia
    0
    0%
    27
    14.4%
    39
    20.5%
    16
    17%
    82
    17%
    North America
    4
    33.3%
    31
    16.6%
    32
    16.8%
    16
    17%
    83
    17.2%
    Europe
    8
    66.7%
    129
    69%
    119
    62.6%
    62
    66%
    318
    65.8%
    ECOG Performance Status (Count of Participants)
    Performance Status = 0
    3
    25%
    37
    19.8%
    40
    21.1%
    19
    20.2%
    99
    20.5%
    Performance Status = 1
    9
    75%
    150
    80.2%
    150
    78.9%
    75
    79.8%
    384
    79.5%
    Tobacco Use (Count of Participants)
    No
    0
    0%
    22
    11.8%
    12
    6.3%
    12
    12.8%
    46
    9.5%
    Yes
    12
    100%
    165
    88.2%
    178
    93.7%
    82
    87.2%
    437
    90.5%
    Body Surface Area (m^2) (m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m^2]
    26.40
    (4.42)
    25.84
    (5.01)
    25.95
    (4.91)
    25.54
    (4.89)
    25.82
    (4.94)

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    Description OS will be derived as: (date of death - date of randomization) + 1. Subjects who are alive or permanently lost to follow-up at the cut-off date for the analysis will be censored at the last date the subject was known to be alive.
    Time Frame Up to approximately 2.5 years

    Outcome Measure Data

    Analysis Population Description
    The analysis population was based on the Intent to Treat (ITT) Analysis Set, which per the Statistical Analysis Plan was defined as all subjects randomized in Part 2 of the study, as assigned to treatment (i.e., n = 471). As such, these results do not include the subjects enrolled in Part 1 of the study.
    Arm/Group Title Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    Measure Participants 187 190 94
    Median (95% Confidence Interval) [months]
    6.9
    7.0
    7.4
    2. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS will be defined as the time from the date of randomization to the date of first documentation of tumor progression or death from any cause, whichever occurs first.
    Time Frame Up to approximately 2.5 years

    Outcome Measure Data

    Analysis Population Description
    The analysis population was based on the Intent to Treat (ITT) Analysis Set, which per the Statistical Analysis Plan was defined as all subjects randomized in Part 2 of the study, as assigned to treatment (i.e., n = 471). As such, these results do not include the subjects enrolled in Part 1 of the study.
    Arm/Group Title Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    Measure Participants 187 190 94
    Median (95% Confidence Interval) [months]
    3.5
    3.0
    3.4
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description The ORR is the percentage of subjects with best overall response of either complete response (CR) or partial response (PR); ORR = CR + PR. Per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters as confirmed by CT or MRI.
    Time Frame Up to approximately 2.5 years

    Outcome Measure Data

    Analysis Population Description
    The analysis population was based on the Intent to Treat (ITT) Analysis Set, which per the Statistical Analysis Plan was defined as all subjects randomized in Part 2 of the study, as assigned to treatment (i.e., n = 471). As such, these results do not include the subjects enrolled in Part 1 of the study.
    Arm/Group Title Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    Measure Participants 187 190 94
    Count of Participants [Participants]
    32
    266.7%
    36
    19.3%
    19
    10%
    4. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description The CBR is defined as the percentage of subjects with either a CR, PR, or stable disease (SD), relative to the number of subjects in the treatment group. Per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, CR was defined as the disappearance of all target lesions; PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study, as confirmed by CT or MRI .
    Time Frame Up to approximately 2.5 years

    Outcome Measure Data

    Analysis Population Description
    The analysis population was based on the Intent to Treat (ITT) Analysis Set, which per the Statistical Analysis Plan was defined as all subjects randomized in Part 2 of the study, as assigned to treatment (i.e., n = 471). As such, these results do not include the subjects enrolled in Part 1 of the study.
    Arm/Group Title Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    Measure Participants 187 190 94
    Count of Participants [Participants]
    126
    1050%
    112
    59.9%
    64
    33.7%

    Adverse Events

    Time Frame Adverse events (AEs) were collected for all enrolled subjects beginning with first dose of study medication. Serious adverse events (and AEs based on local regulations) were to be collected starting on the day of written informed consent. In addition to reporting while on study therapy, adverse events were required to be reported through 30 days after the last dose of study therapy.
    Adverse Event Reporting Description AEs were collected via Investigator assessment and laboratory testing during routine visits as required per protocol. For the analyses, All-Cause Mortality was evaluated for all subjects enrolled in Part 1 or randomized in Part 2 of the study and assigned treatment (n = 483). All other Safety Analyses, including Serious Adverse Events and Other Adverse Events, were evaluated using the Safety Analysis Set, defined as all subjects who received at least 1 dose of study medication (n = 470).
    Arm/Group Title Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Arm/Group Description Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Dinutuximab (16 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 or Grade 2/3 that in the view of the Investigator is adequately managed and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV. Dinutuximab: Dinutuximab injection, for intravenous (IV) use Irinotecan: Irinotecan injection, IV infusion Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Irinotecan: Irinotecan injection, IV infusion Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle. Topotecan: Topotecan for injection
    All Cause Mortality
    Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/12 (83.3%) 158/187 (84.5%) 159/190 (83.7%) 84/94 (89.4%)
    Serious Adverse Events
    Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/12 (41.7%) 74/183 (40.4%) 76/187 (40.6%) 39/88 (44.3%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/12 (0%) 8/183 (4.4%) 17/187 (9.1%) 3/88 (3.4%)
    Neutropenia 1/12 (8.3%) 7/183 (3.8%) 7/187 (3.7%) 4/88 (4.5%)
    Anemia 0/12 (0%) 4/183 (2.2%) 2/187 (1.1%) 6/88 (6.8%)
    Febrile bone marrow aplasia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 1/88 (1.1%)
    Leukocytosis 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Leukopenia 0/12 (0%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    Lymphopenia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Pancytopenia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Thrombocytopenia 0/12 (0%) 0/183 (0%) 0/187 (0%) 7/88 (8%)
    Cardiac disorders
    Atrial fibrillation 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)
    Bradycardia 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Cardio-respiratory arrest 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Coronary artery disease 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Endocarditis noninfective 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Myocardial infarction 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Pericardial effusion 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Acute coronary syndrome 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 1/88 (1.1%)
    Acute myocardial infarction 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Atrial flutter 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Cardiac failure 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Supraventricular tachycardia 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Gastrointestinal disorders
    Diarrhea 2/12 (16.7%) 8/183 (4.4%) 17/187 (9.1%) 1/88 (1.1%)
    Vomiting 0/12 (0%) 6/183 (3.3%) 9/187 (4.8%) 1/88 (1.1%)
    Abdominal pain 0/12 (0%) 4/183 (2.2%) 3/187 (1.6%) 2/88 (2.3%)
    Abdominal pain upper 0/12 (0%) 3/183 (1.6%) 0/187 (0%) 0/88 (0%)
    Nausea 0/12 (0%) 3/183 (1.6%) 3/187 (1.6%) 1/88 (1.1%)
    Abdominal distension 0/12 (0%) 1/183 (0.5%) 2/187 (1.1%) 0/88 (0%)
    Colitis 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Constipation 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Dysphagia 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Gastrointestinal toxicity 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Neutropenic colitis 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 1/88 (1.1%)
    Pancreatitis 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Duodenal perforation 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Enteritis 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Ileus 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Oesophagitis 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    General disorders
    Asthenia 0/12 (0%) 4/183 (2.2%) 1/187 (0.5%) 1/88 (1.1%)
    Chest pain 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Pain 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Chest discomfort 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Death 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 1/88 (1.1%)
    Malaise 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Pyrexia 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Fatigue 0/12 (0%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    General physical health deterioration 0/12 (0%) 0/183 (0%) 5/187 (2.7%) 0/88 (0%)
    Non-cardiac chest pain 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Sudden death 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Hepatobiliary disorders
    Acute hepatic failure 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Cholelithiasis 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Infections and infestations
    Pneumonia 1/12 (8.3%) 6/183 (3.3%) 9/187 (4.8%) 5/88 (5.7%)
    Sepsis 0/12 (0%) 3/183 (1.6%) 3/187 (1.6%) 0/88 (0%)
    Respiratory tract infection 0/12 (0%) 2/183 (1.1%) 1/187 (0.5%) 1/88 (1.1%)
    Clostridium difficile infection 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Cystitis 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Lower respiratory tract infection 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Neutropenic sepsis 0/12 (0%) 1/183 (0.5%) 2/187 (1.1%) 0/88 (0%)
    Septic shock 1/12 (8.3%) 1/183 (0.5%) 3/187 (1.6%) 0/88 (0%)
    Bronchitis 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 2/88 (2.3%)
    Clostridium difficile colitis 1/12 (8.3%) 0/183 (0%) 4/187 (2.1%) 0/88 (0%)
    Escherichia bacteraemia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Gastroenteritis pseudomonas 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Herpes zoster 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Influenza 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Klebsiella sepsis 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Pneumocystis jirovecii pneumonia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Pyelonephritis 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Upper respiratory tract infection 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Injury, poisoning and procedural complications
    Craniocerebral injury 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Humerus fracture 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Subdural haematoma 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Traumatic intracranial haemorrhage 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Investigations
    Neutrophil count decreased 0/12 (0%) 2/183 (1.1%) 4/187 (2.1%) 3/88 (3.4%)
    Alanine aminotransferase increased 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Amylase increased 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Aspartate aminotransferase increased 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Lipase increased 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    White blood cell count decreased 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Blood creatinine increased 1/12 (8.3%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Ejection fraction decreased 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Platelet count decreased 0/12 (0%) 0/183 (0%) 0/187 (0%) 5/88 (5.7%)
    Troponin I increased 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/12 (0%) 5/183 (2.7%) 2/187 (1.1%) 1/88 (1.1%)
    Dehydration 0/12 (0%) 3/183 (1.6%) 4/187 (2.1%) 0/88 (0%)
    Decreased appetite 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Hypercalcaemia 1/12 (8.3%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Hypoglycaemia 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Hypokalaemia 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 1/88 (1.1%)
    Failure to thrive 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Hyperglycaemia 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Hypomagnesaemia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Tumour lysis syndrome 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Back pain 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Muscular weakness 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Intervertebral disc protrusion 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Musculoskeletal pain 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Small cell lung cancer 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 2/88 (2.3%)
    Cancer pain 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Malignant pleural effusion 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Metastases to central nervous system 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Tumour pain 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Nervous system disorders
    Seizure 0/12 (0%) 2/183 (1.1%) 1/187 (0.5%) 0/88 (0%)
    Syncope 0/12 (0%) 2/183 (1.1%) 1/187 (0.5%) 0/88 (0%)
    Haemorrhagic stroke 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Neurological decompensation 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Neuropathy peripheral 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Tremor 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Dyskinesia 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Headache 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Psychiatric disorders
    Confusional state 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Anxiety 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Renal and urinary disorders
    Dysuria 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Acute kidney injury 1/12 (8.3%) 0/183 (0%) 3/187 (1.6%) 0/88 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Dyspnoea 0/12 (0%) 2/183 (1.1%) 1/187 (0.5%) 4/88 (4.5%)
    Pulmonary haemorrhage 0/12 (0%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Bronchospasm 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Lung consolidation 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Respiratory failure 0/12 (0%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    Acute respiratory distress syndrome 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Acute respiratory failure 1/12 (8.3%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    Chronic obstructive pulmonary disease 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 2/88 (2.3%)
    Hypoxia 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 1/88 (1.1%)
    Pleural effusion 0/12 (0%) 0/183 (0%) 0/187 (0%) 2/88 (2.3%)
    Pleuritic pain 0/12 (0%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Pneumonitis 0/12 (0%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    Pneumothorax 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Pulmonary embolism 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 2/88 (2.3%)
    Skin and subcutaneous tissue disorders
    Pruritus 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Urticaria 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Vascular disorders
    Hypotension 0/12 (0%) 3/183 (1.6%) 2/187 (1.1%) 0/88 (0%)
    Hypovolaemic shock 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Shock haemorrhagic 0/12 (0%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Embolism 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Peripheral arterial occlusive disease 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)
    Superior vena cava occlusion 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Superior vena cava syndrome 0/12 (0%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: Dinutuximab + Irinotecan Part 2: Dinutuximab + Irinotecan Part 2: Irinotecan Part 2: Topotecan
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/12 (100%) 183/183 (100%) 183/187 (97.9%) 86/88 (97.7%)
    Blood and lymphatic system disorders
    Anaemia 3/12 (25%) 67/183 (36.6%) 55/187 (29.4%) 58/88 (65.9%)
    Neutropenia 4/12 (33.3%) 59/183 (32.2%) 47/187 (25.1%) 45/88 (51.1%)
    Leukopenia 0/12 (0%) 30/183 (16.4%) 22/187 (11.8%) 12/88 (13.6%)
    Thrombocytopenia 0/12 (0%) 18/183 (9.8%) 13/187 (7%) 22/88 (25%)
    Febrile neutropenia 0/12 (0%) 11/183 (6%) 18/187 (9.6%) 4/88 (4.5%)
    Cardiac disorders
    Atrial fibrillation 1/12 (8.3%) 1/183 (0.5%) 2/187 (1.1%) 0/88 (0%)
    Gastrointestinal disorders
    Diarrhoea 10/12 (83.3%) 118/183 (64.5%) 116/187 (62%) 13/88 (14.8%)
    Abdominal pain 5/12 (41.7%) 82/183 (44.8%) 24/187 (12.8%) 9/88 (10.2%)
    Nausea 7/12 (58.3%) 81/183 (44.3%) 88/187 (47.1%) 22/88 (25%)
    Vomiting 5/12 (41.7%) 65/183 (35.5%) 57/187 (30.5%) 6/88 (6.8%)
    Abdominal pain upper 2/12 (16.7%) 30/183 (16.4%) 11/187 (5.9%) 5/88 (5.7%)
    Constipation 4/12 (33.3%) 16/183 (8.7%) 16/187 (8.6%) 13/88 (14.8%)
    Dysphagia 1/12 (8.3%) 6/183 (3.3%) 3/187 (1.6%) 0/88 (0%)
    Gastrooesophageal reflux disease 1/12 (8.3%) 4/183 (2.2%) 4/187 (2.1%) 1/88 (1.1%)
    Stomatitis 1/12 (8.3%) 4/183 (2.2%) 9/187 (4.8%) 6/88 (6.8%)
    Abdominal pain lower 1/12 (8.3%) 3/183 (1.6%) 2/187 (1.1%) 0/88 (0%)
    Dry mouth 1/12 (8.3%) 3/183 (1.6%) 4/187 (2.1%) 1/88 (1.1%)
    Flatulence 1/12 (8.3%) 1/183 (0.5%) 1/187 (0.5%) 0/88 (0%)
    General disorders
    Asthenia 4/12 (33.3%) 44/183 (24%) 39/187 (20.9%) 25/88 (28.4%)
    Fatigue 3/12 (25%) 36/183 (19.7%) 48/187 (25.7%) 16/88 (18.2%)
    Non-cardiac chest pain 1/12 (8.3%) 24/183 (13.1%) 8/187 (4.3%) 5/88 (5.7%)
    Pyrexia 2/12 (16.7%) 19/183 (10.4%) 10/187 (5.3%) 13/88 (14.8%)
    Pain 0/12 (0%) 13/183 (7.1%) 5/187 (2.7%) 1/88 (1.1%)
    Chest pain 1/12 (8.3%) 11/183 (6%) 5/187 (2.7%) 1/88 (1.1%)
    Chest discomfort 1/12 (8.3%) 5/183 (2.7%) 2/187 (1.1%) 0/88 (0%)
    Discomfort 1/12 (8.3%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Infections and infestations
    Pneumonia 1/12 (8.3%) 12/183 (6.6%) 11/187 (5.9%) 9/88 (10.2%)
    Upper respiratory tract infection 1/12 (8.3%) 5/183 (2.7%) 10/187 (5.3%) 2/88 (2.3%)
    Septic shock 1/12 (8.3%) 2/183 (1.1%) 3/187 (1.6%) 0/88 (0%)
    Bronchitis 1/12 (8.3%) 1/183 (0.5%) 3/187 (1.6%) 3/88 (3.4%)
    Clostridium difficile colitis 1/12 (8.3%) 0/183 (0%) 4/187 (2.1%) 0/88 (0%)
    Investigations
    Weight decreased 1/12 (8.3%) 24/183 (13.1%) 25/187 (13.4%) 8/88 (9.1%)
    Blood lactate dehydrogenase increased 0/12 (0%) 19/183 (10.4%) 6/187 (3.2%) 5/88 (5.7%)
    Neutrophil count decreased 1/12 (8.3%) 18/183 (9.8%) 28/187 (15%) 23/88 (26.1%)
    Alanine aminotransferase increased 0/12 (0%) 12/183 (6.6%) 13/187 (7%) 8/88 (9.1%)
    Aspartate aminotransferase increased 0/12 (0%) 10/183 (5.5%) 11/187 (5.9%) 8/88 (9.1%)
    Platelet count decreased 1/12 (8.3%) 10/183 (5.5%) 6/187 (3.2%) 18/88 (20.5%)
    Blood alkaline phosphatase increased 0/12 (0%) 7/183 (3.8%) 6/187 (3.2%) 5/88 (5.7%)
    White blood cell count decreased 0/12 (0%) 6/183 (3.3%) 12/187 (6.4%) 14/88 (15.9%)
    Lymphocyte count decreased 0/12 (0%) 5/183 (2.7%) 4/187 (2.1%) 5/88 (5.7%)
    Blood creatinine increased 1/12 (8.3%) 3/183 (1.6%) 4/187 (2.1%) 1/88 (1.1%)
    Clostridium test positive 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)
    Haemoglobin decreased 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 2/88 (2.3%)
    Metabolism and nutrition disorders
    Decreased appetite 5/12 (41.7%) 60/183 (32.8%) 58/187 (31%) 23/88 (26.1%)
    Hypokalaemia 1/12 (8.3%) 18/183 (9.8%) 16/187 (8.6%) 4/88 (4.5%)
    Hyponatraemia 0/12 (0%) 14/183 (7.7%) 17/187 (9.1%) 2/88 (2.3%)
    Dehydration 2/12 (16.7%) 10/183 (5.5%) 14/187 (7.5%) 1/88 (1.1%)
    Hyperglycaemia 0/12 (0%) 8/183 (4.4%) 4/187 (2.1%) 9/88 (10.2%)
    Hypomagnesaemia 3/12 (25%) 7/183 (3.8%) 9/187 (4.8%) 4/88 (4.5%)
    Hypoalbuminaemia 0/12 (0%) 6/183 (3.3%) 11/187 (5.9%) 0/88 (0%)
    Hypocalcaemia 1/12 (8.3%) 6/183 (3.3%) 3/187 (1.6%) 1/88 (1.1%)
    Hypercalcaemia 1/12 (8.3%) 1/183 (0.5%) 0/187 (0%) 0/88 (0%)
    Hypercholesterolaemia 1/12 (8.3%) 0/183 (0%) 1/187 (0.5%) 1/88 (1.1%)
    Hypertriglyceridaemia 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 1/88 (1.1%)
    Musculoskeletal and connective tissue disorders
    Back pain 6/12 (50%) 47/183 (25.7%) 11/187 (5.9%) 6/88 (6.8%)
    Pain in extremity 3/12 (25%) 31/183 (16.9%) 5/187 (2.7%) 3/88 (3.4%)
    Musculoskeletal pain 1/12 (8.3%) 16/183 (8.7%) 8/187 (4.3%) 2/88 (2.3%)
    Myalgia 0/12 (0%) 13/183 (7.1%) 3/187 (1.6%) 2/88 (2.3%)
    Musculoskeletal chest pain 2/12 (16.7%) 12/183 (6.6%) 3/187 (1.6%) 3/88 (3.4%)
    Arthralgia 2/12 (16.7%) 11/183 (6%) 2/187 (1.1%) 4/88 (4.5%)
    Flank pain 1/12 (8.3%) 5/183 (2.7%) 2/187 (1.1%) 0/88 (0%)
    Muscular weakness 1/12 (8.3%) 2/183 (1.1%) 10/187 (5.3%) 3/88 (3.4%)
    Neck pain 1/12 (8.3%) 2/183 (1.1%) 3/187 (1.6%) 2/88 (2.3%)
    Nervous system disorders
    Headache 2/12 (16.7%) 21/183 (11.5%) 12/187 (6.4%) 4/88 (4.5%)
    Dizziness 0/12 (0%) 12/183 (6.6%) 15/187 (8%) 6/88 (6.8%)
    Neuropathy peripheral 2/12 (16.7%) 3/183 (1.6%) 1/187 (0.5%) 0/88 (0%)
    Restless legs syndrome 1/12 (8.3%) 2/183 (1.1%) 0/187 (0%) 0/88 (0%)
    Psychiatric disorders
    Anxiety 1/12 (8.3%) 6/183 (3.3%) 2/187 (1.1%) 2/88 (2.3%)
    Confusional state 1/12 (8.3%) 3/183 (1.6%) 2/187 (1.1%) 2/88 (2.3%)
    Agitation 1/12 (8.3%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/12 (8.3%) 2/183 (1.1%) 6/187 (3.2%) 1/88 (1.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 4/12 (33.3%) 28/183 (15.3%) 16/187 (8.6%) 9/88 (10.2%)
    Dyspnoea 0/12 (0%) 27/183 (14.8%) 18/187 (9.6%) 13/88 (14.8%)
    Productive cough 1/12 (8.3%) 11/183 (6%) 6/187 (3.2%) 3/88 (3.4%)
    Dysphonia 1/12 (8.3%) 8/183 (4.4%) 4/187 (2.1%) 1/88 (1.1%)
    Chronic obstructive pulmonary disease 1/12 (8.3%) 1/183 (0.5%) 2/187 (1.1%) 2/88 (2.3%)
    Rhinorrhoea 1/12 (8.3%) 1/183 (0.5%) 2/187 (1.1%) 0/88 (0%)
    Acute respiratory failure 1/12 (8.3%) 0/183 (0%) 2/187 (1.1%) 0/88 (0%)
    Epistaxis 1/12 (8.3%) 0/183 (0%) 2/187 (1.1%) 1/88 (1.1%)
    Respiratory tract congestion 1/12 (8.3%) 0/183 (0%) 1/187 (0.5%) 0/88 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/12 (8.3%) 49/183 (26.8%) 33/187 (17.6%) 10/88 (11.4%)
    Rash 2/12 (16.7%) 4/183 (2.2%) 4/187 (2.1%) 1/88 (1.1%)
    Erythema 1/12 (8.3%) 2/183 (1.1%) 1/187 (0.5%) 0/88 (0%)
    Livedo reticularis 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)
    Palmar erythema 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)
    Vascular disorders
    Hypotension 1/12 (8.3%) 15/183 (8.2%) 9/187 (4.8%) 5/88 (5.7%)
    Hypertension 1/12 (8.3%) 14/183 (7.7%) 4/187 (2.1%) 3/88 (3.4%)
    Flushing 1/12 (8.3%) 4/183 (2.2%) 0/187 (0%) 0/88 (0%)
    Peripheral arterial occlusive disease 1/12 (8.3%) 0/183 (0%) 0/187 (0%) 0/88 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Prior to submission for any public disclosure of the data or results, the Institution and Principal Investigator shall provide Sponsor with at least 60 days for review of the Publication. In addition, the Institution and Principal Investigator agree that the first Publication of the results shall be made as a joint, multicenter publication coordinated by Sponsor, with investigators and institutions from all participating sites contributing data.

    Results Point of Contact

    Name/Title Program Manager, Oncology
    Organization United Therapeutics Corporation
    Phone 919-485-8350
    Email kmaher@unither.com
    Responsible Party:
    United Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03098030
    Other Study ID Numbers:
    • DIV-SCLC-301
    First Posted:
    Mar 31, 2017
    Last Update Posted:
    Dec 9, 2020
    Last Verified:
    Nov 1, 2020