BRIGHTER: A Study of BBI608 Plus Weekly Paclitaxel to Treat Gastric and Gastro-Esophageal Junction Cancer

Sponsor
Sumitomo Pharma Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02178956
Collaborator
(none)
714
263
2
35.6
2.7
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether it is better to receive a new drug, BBI608, in addition to paclitaxel chemotherapy or better to receive paclitaxel chemotherapy alone as second line treatment for gastric and gastroesophageal junction cancer after prior first line platinum and fluoropyrimidine based chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The goal of this study is to determine if paclitaxel given together with BBI608 as second line therapy will prolong overall survival compared to paclitaxel alone.

Approximately 700 patients will be randomized with histologically or cytologically confirmed metastatic gastric or gastroesophageal junction adenocarcinoma.

Patients must have failed first line therapy with any platinum/fluoropyrimidine doublet.

BBI608/placebo will be administered daily, paclitaxel will be administered i.v. on days 1, 8 and 15 of a 4 weekly cycle.

Study Design

Study Type:
Interventional
Actual Enrollment :
714 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III Clinical Trial of BBI608 Plus Weekly Paclitaxel vs. Placebo Plus Weekly Paclitaxel in Adult Patients With Advanced, Previously Treated Gastric and Gastro-Esophageal Junction Adenocarcinoma
Study Start Date :
Oct 1, 2014
Actual Primary Completion Date :
Sep 20, 2017
Actual Study Completion Date :
Sep 20, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: BBI608 plus Paclitaxel

Drug: BBI608
BBI608 480 mg orally two times daily (960 mg total daily dose)
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
  • Drug: Paclitaxel
    Paclitaxel 80 mg/m2 I.V. infusion on Days 1, 8, and 15 of every 4-week cycle

    Placebo Comparator: Placebo plus Paclitaxel

    Drug: Paclitaxel
    Paclitaxel 80 mg/m2 I.V. infusion on Days 1, 8, and 15 of every 4-week cycle

    Other: Placebo
    Orally two times daily

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [36 months]

      The primary objective of this study is to assess the effect of orally administered BBI608 plus weekly paclitaxel, in comparison to placebo plus weekly paclitaxel on the Overall Survival of patients with advanced histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma who failed treatment with one platinum/fluoropyrimidine containing regimen for unresectable or metastatic disease.

    Secondary Outcome Measures

    1. Progression Free Survival [36 months]

      Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause which comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in anon-target lesion, or the appearance of new lesions.

    2. Objective Response Rate [36 months]

      Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.

    3. Disease Control Rate [36 months]

      Disease control Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR+SD) based on RECIST 1.1.

    4. Number of Patients With Adverse Events [36 months]

      All patients who have received at least one dose of BBI608/Placebo will be included in the safety analysis. The number of patients who experienced at least one adverse event is reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Cytologically or histologically confirmed advanced gastric or GEJ adenocarcinoma that is metastatic or locally advanced and unresectable.

    • Failed treatment with one regimen containing at least a platinum/fluoropyrimidine doublet for unresectable or metastatic disease.Treatment failure is defined as progression of disease (clinical or radiologic) during first line treatment for unresectable or metastatic disease or ≤ 6 months after last dose of first line treatment.

    • Paclitaxel therapy is appropriate for the patient and is recommended by the Investigator.

    • Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 21 days prior to randomization. Patients with either measurable disease OR non-measurable evaluable disease will be eligible.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

    ・≥ 18 years of age.

    • For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 6 months after the final dose of Paclitaxel or for 30 days for female patients and for 90 days for male patients, of the final BBI608/Placebo dose if Paclitaxel was not administered.

    • Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.

    • Alanine transaminase (ALT) ≤ 3 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases] within 14 days prior to randomization.

    • Hemoglobin (Hgb) ≥ 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion within 1 week of baseline Hgb assessment.

    • Total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.

    • Creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min (as calculated by the Cockroft-Gault equation) within 14 days prior to randomization.

    • Absolute neutrophil count ≥ 1.5 x 10^9/L within 14 days prior to randomization.

    • Platelet count ≥ 100 x 10^9/L within 14 days prior to randomization. Must not have required transfusion within 1 week of baseline platelet assessment.

    • Other baseline laboratory evaluations must be done within 14 days prior to randomization.

    • Patient must consent to provision of a representative formalin fixed paraffin block of tumor tissue, if available, in order that the specific correlative marker assays may be conducted.

    • Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.

    • Patients must be accessible for treatment and follow up.

    • Protocol treatment is to begin within 2 working days of patient randomization.

    • The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.

    Exclusion Criteria:
    • Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of BBI608/placebo within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of BBI608/placebo.Radiotherapy, immunotherapy, or investigational agents within four weeks of first planned dose of BBI608/placebo, with the exception of a single dose of radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before randomization.

    • Prior taxanes in the neoadjuvant or adjuvant setting with progression occurring within 6 months of completion of taxane therapy; or any taxanes in the metastatic setting.

    • More than one prior chemotherapy regimen administered in the metastatic setting.

    • Major surgery within 4 weeks prior to randomization.

    • Any known symptomatic brain metastases requiring steroids.

    • Women who are pregnant or breastfeeding.

    • Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent.

    • Unable or unwilling to swallow BBI608/placebo capsules daily.

    • Uncontrolled intercurrent illness.

    • Peripheral neuropathy ≥ CTCAE Grade 2 at baseline.

    • History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 3 years.

    • Prior treatment with BBI608.

    • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.

    • Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic - Arizona Scottsdale Arizona United States 85259
    2 Colorado Cancer Research Program Denver Colorado United States 80222
    3 Indiana University Health Goshen Center For Cancer Care Goshen Indiana United States 46526
    4 Northern Indiana Cancer Research Consortium South Bend Indiana United States 46628
    5 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    6 Cancer Center of Kansas Wichita Kansas United States 67214
    7 Ochsner NCI CORP New Orleans Louisiana United States 70121
    8 Spectrum Health Butterworth Grand Rapids Michigan United States 49503
    9 Munson Medical Center Traverse City Michigan United States 49684
    10 Mayo Clinic - Rochester Rochester Minnesota United States 55905
    11 Metro-Minnesota NCI CORP Saint Louis Park Minnesota United States 55416
    12 Heartland NCORP Saint Louis Missouri United States 63131
    13 New Hampshire Oncology Hematology - Concord Concord New Hampshire United States 03106
    14 New Hampshire Oncology Hematology - Laconia Laconia New Hampshire United States 03246
    15 Weill Medical College of Cornell University New York New York United States 10065
    16 State University of New York Upstate Medical University Syracuse New York United States 13210
    17 Indiana University Health University Hospital Chapel Hill North Carolina United States 27516
    18 Ohio State University Medical Center Columbus Ohio United States 43210
    19 The University of Oklahoma Health Sciences Center (OUHSC) Oklahoma City Oklahoma United States 73104
    20 Geisinger Medical Center Danville Pennsylvania United States 17822
    21 Virginia Mason Medical Center Seattle Washington United States 98101
    22 Swedish Cancer Institute/ Swedish Health Services Seattle Washington United States 98104
    23 Saint Vincent Hospital CCOP Green Bay Wisconsin United States 54301
    24 St. Mary's Hospital Green Bay Wisconsin United States 54307
    25 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    26 Marshfield CCOP Marshfield Wisconsin United States 54449
    27 Bankstown-Lidcombe Bankstown New South Wales Australia 2200
    28 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    29 St Vincent's Hospital Darlinghurst New South Wales Australia 2010
    30 Central coast area health (public) Gosford New South Wales Australia 2250
    31 Port Macquaries Base Hospital Port Macquarie New South Wales Australia 2444
    32 Royal North Shore Hospital St Leonards New South Wales Australia 2065
    33 Riverina Cancer Care Centre Wagga Wagga New South Wales Australia 2650
    34 Royal Brisbane & Women's Hospital Herston Queensland Australia 4029
    35 Sunshine Coast Hospital and Health Service Nambour Queensland Australia 4560
    36 Gold Coast University Hospital Southport Queensland Australia 4215
    37 Townsville Hospital Townsville Queensland Australia 4814
    38 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    39 Flinders Medical Centre Bedford Park South Australia Australia 5042
    40 Ashford Cancer Centre Research Kurralta Park South Australia Australia 5037
    41 The Queen Elizabeth Hospital Woodville South Australia Australia 5011
    42 Bendigo Hospital Bendigo Victoria Australia 3550
    43 Monash Health East Bentleigh Victoria Australia 3165
    44 Peninsula & South Eastern Haematology and Oncology Group East Bentleigh Victoria Australia 3165
    45 St Vincent's Hospital Fitzroy Victoria Australia 3065
    46 Austin Hospital Heidelberg Victoria Australia 3084
    47 Ballarat base hospital Heidelberg Victoria Australia 3084
    48 Royal Melbourne Hospital Parkville Victoria Australia 3050
    49 Sunshine Hospital St Albans Victoria Australia 3021
    50 Ballarat Oncology and Haematology Services Wendouree Victoria Australia 3355
    51 Fiona Stanley Hospital Subiaco Western Australia Australia 6008
    52 Imelda Ziekenhuis Bonheiden Antwerpen Belgium 2820
    53 UZ Antwerpen Edegem Antwerpen Belgium 2650
    54 UZ Brussel - Campus Jette Brussel Brussels Capital Region Belgium 1090
    55 Institut Jules Bordet Bruxelles Brussels Capital Region Belgium 1000
    56 Cliniques Universitaires Saint-Luc Bruxelles Brussels Capital Region Belgium B-1200
    57 CHU Ambroise Paré Mons Hainaut Belgium 7000
    58 UZ Leuven - Campus Gasthuisberg Leuven Vlaams Brabant Belgium 3000
    59 AZ Sint-Lucas - Campus Sint-Lucas Brugge (Assebroek) Belgium 8310
    60 CHU de Liège - Domaine Universitaire du Sart Tilman Liège Belgium 4000
    61 Oncovida - Centro de Oncologia da Bahia Salvador Bahia Brazil 41820021
    62 Instituto do Câncer do Ceará - Instituto do Câncer do Cear Fortaleza Ceará Brazil 60430-230
    63 Cetus Hospital Dia Oncologia Belo Horizonte Minas Gerais Brazil 30150-270
    64 Hospital Erasto Gaertner Curitiba Paraná Brazil 81520-060
    65 Hospital Bruno Born Lajeado Rio Grande Do Sul Brazil 95900000
    66 Hospital da Cidade de Passo Fundo Passo Fundo Rio Grande Do Sul Brazil 99010-260
    67 UPCO - Unidade de Pesquisa Clinica em Oncologia LTDA Pelotas Rio Grande Do Sul Brazil 96015-280
    68 Clinica de Neoplasias Litoral Itajai Santa Catarina Brazil 88301-220
    69 Fundaçao dr Amaral Carvalho Jaú São Paulo Brazil 17210-080
    70 Hospital de Base de São José do Rio Preto São José do Rio Preto São Paulo Brazil 15090-000
    71 Inca-RJ Rio de Janeiro Brazil 20231-050
    72 IEP São Lucas São Paulo Brazil 01236030
    73 Casa de Saúde Santa Marcelina São Paulo Brazil 08270-070
    74 Specialised Hospital for Active Treatment in Oncology Sofia Sofia-Grad Bulgaria 1756
    75 UMHAT ""Dr. Georgi Stranski"" Dept. Medical Oncology Pleven Bulgaria 5800
    76 District Dispensery with Stationary - Sofia District Sofia Bulgaria 1233
    77 Multiprofile hospital for active treatment Sofia Bulgaria 1233
    78 UMHAT"Sv.Ivan Rilski" Sofia Bulgaria 1606
    79 Uni. Multiprofile Hospital for Active treatment Sveta Marina Varna Bulgaria 9010
    80 COC - Vratsa Dept. of Palliative Care Vratsa Bulgaria 3000
    81 The Ottawa Hospital Cancer Centre Ottawa Ontario Canada K1H 8L6
    82 Saint Michael's Hospital Li Ka Shing Knowledge Institute Toronto Ontario Canada M5B 1W8
    83 Mount Sinai Hospital Toronto Ontario Canada M5G 1X5
    84 Princess Margaret Hospital Toronto Ontario Canada M5G 2C4
    85 Hopital Notre-Dame du CHUM Montreal Quebec Canada H2L 2W5
    86 McGill University Health Centre - Montreal General Hospital Montreal Quebec Canada H3G 1A4
    87 Cancer Hospital Chinese Academy of Medical Sciences Beijing Beijing China 100021
    88 The 307th Hospital of Chinese People's Liberation Army Beijing Beijing China 100071
    89 Beijing Cancer Hospital Beijing Beijing China 100142
    90 Chinese PLA General Hospital Beijing Beijing China 100853
    91 Fujian Medical University Union Hospital Fuzhou Fujian China 350001
    92 Sun Yat-Sen University Cancer Center Guangzhou Guangdong China 510060
    93 Southern Medical University, Nanfang Hospital Guangzhou Guangdong China 510515
    94 Harbin Medical University Cancer Hospital Heilongjiang Heilongjiang China 150081
    95 The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China 450003
    96 Henan Cancer Hospital Zhengzhou Henan China 450008
    97 Hunan Cancer Hospital Changsha Hunan China 410006
    98 The 81 Hospital of the Chinese People's Liberation Army Nanjing Jiangsu China 210002
    99 Jiang Su Cancer Hospital Nanjing Jiangsu China 210009
    100 Jiangsu Province Hospital Nanjing Jiangsu China 210029
    101 The First Bethune Hospital of Jilin University Changchun Jilin China 130021
    102 Jilin Cancer Hospital Jilin Jilin China 130021
    103 The First Hospital of China Medical University Shenyang Liaoning China 110002
    104 General Hospital of Ningxia Medical University Yinchuan Ningxia China 750004
    105 Fudan University Shanghai Cancer Center Shanghai Shanghai China 200032
    106 Zhongshan Hospital Shanghai Shanghai China 200032
    107 West China Hospital, Sichuan University Chengdu Sichuan China 610041
    108 Tianjin Medical University Cancer Institute & Hospital Tianjin Tianjin China 300202
    109 Xin Jiang Tumor Hospital, Xin Jiang Medical University Urumqi Xinjiang China 830000
    110 Sir Run Run Shaw Hospital School of Medicine, Zhejiang University Hangzhou Zhejiang China 310016
    111 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    112 Tongji Hospital Wuhan China 430030
    113 FN Hradec Kralove Hradec Kralove Královéhradecký Kraj Czechia 500 05
    114 Fakultni nemocnice Olomouc Olomouc Olomoucký Kraj Czechia 775 20
    115 Masarykuv onkologicky ustav Brno Czechia 656 53
    116 Vseobecna fakultni nemocnice v Praze Praha 2 Czechia 128 08
    117 Nemocnice Na Bulovce Praha 8 Czechia 180 81
    118 East Tallinn Central Hospital Oncology Center Tallinn Harjumaa Estonia 10138
    119 Tartu University Hospital Clinic of Hematology and Oncology Tartu Tartumaa Estonia 51014
    120 Centre Antoine Lacassagne Nice Alpes-Maritimes France 06189 Cedex 2
    121 Hopital Saint Joseph - Marseille Marseille Bouches-du-Rhône France 13008
    122 Centre Paul Papin St Herblain Cedex Loire-Atlantique France 44805
    123 Centre Rene Gauducheau St Herblain Cedex Loire-Atlantique France 44805
    124 Hopital Privé Jean Mermoz Lyon Rhône France 69008
    125 Chd Vendee La Roche Sur Yon La Roche sur Yon Cedex 9 Vendée France 85925
    126 Hospital of Poitiers Poitiers Vienne France 86021
    127 Hôpital Morvan - CHRU de Brest Brest Cedex France 29609
    128 CHU Estaing Clermont-Ferrand France 63003
    129 CHU - Hôpital De La Timone Marseille France 13385
    130 Centre Hospitalier De Mont De Marsan - Hopital Layné Mont de Marsan Cedex France 40024
    131 Centre eugène marquis Rennes France 35042
    132 CHU Saint Etienne Saint Etienne France 42270
    133 Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Toulouse cedex France 31052
    134 Institut Gustave Roussy Villejuif France 94800
    135 Klinikum Bogenhausen München Bayern Germany 81925
    136 Klinikum der Johann Wolfgang Goethe-Universität Frankfurt/Main Hessen Germany 60596
    137 Ev. Krankenhaus Bielefeld Bielefeld Nordrhein-Westfalen Germany 33611
    138 Kliniken Essen-Mitte Evang. Huyssens-Stiftung Essen Nordrhein-Westfalen Germany 45136
    139 Johannes Gutenberg-Universitaet Maintz Rheinland-Pfalz Germany 55101
    140 Universitätsklinik Carl-Gustav-Carus Dresden Dresden Sachsen Germany 1307
    141 Universitätsklinikum Leipzig Leipzig Sachsen Germany 4103
    142 Charite - Campus Benjamin Franklin (Cbf) Berlin Germany 12200
    143 Charite Berlin Germany 13353
    144 Klinikum Esslingen Esslingen Germany 73730
    145 Facharztzentrum Eppendorf Hamburg Germany 20249
    146 OncoResearch Lerchenfeld GmbH Hamburg Germany 22081
    147 Pécsi Tudományegyetem Klinikai Központ Pécs Baranya Hungary 7624
    148 Békés Megyei Pándy Kálmán Kórház Gyula Békés Hungary 5700
    149 Petz Aladár Megyei Oktató Kórház Gyor Gyor-Moson-Sopron Hungary 9024
    150 Debreceni Egyetem Klinikai Központ Debrecen Hajdú-Bihar Hungary H-4032
    151 Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház- Rendelőinté Szolnok Jász-Nagykun-Szolnok Hungary 5004
    152 Josa Andras Oktato Korhaza Nyiregyhaza Szabolcs-Szatmár-Bereg Hungary 4400
    153 Semmelweis Egyetem Budapest Hungary 1083
    154 Egyesített Szent István és Szent László Kórház-Rendelőintéze Budapest Hungary 1097
    155 Országos Onkológiai Intézet Budapest Hungary 1122
    156 Semmelweis Egyetem Budapest Hungary 1125
    157 Somogy Megyei Kaposi Mór Oktató Kórház Kaposvár Hungary 7400
    158 Soroka Medical Center [Oncology] Beer Sheva HaDarom Israel 84101
    159 The E. Wolfson Medical Center [Oncology] Holon HaMerkaz Israel 58100
    160 Meir Medical Center Kfar Saba HaMerkaz Israel 44281
    161 Rabin Medical Center - Beilinson Hospital Petah Tikva HaMerkaz Israel 49100
    162 Tel Aviv Sourasky Medical Center Tel Aviv Tel-Aviv Israel 64239
    163 Hadassah Medical Organisation Jerusalem Yerushalayim Israel 91120
    164 Rambam Health Care Campus Haifa Israel 31096
    165 Irccs Irst Meldola Forli Italy 47014
    166 AUSL della Romagna, Osp. degli Infermi Faenza Ravenna Italy 48018
    167 Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc Ancona Italy 60126
    168 IRCCS Ospedale Oncologico "Giovanni Paolo II" Bari Italy 701264
    169 Humanitas Gavazzeni Bergamo Italy 24125
    170 Policlinico S.Orsola Malpighi, AOU di Bologna Bologna Italy 40138
    171 PO Garibaldi-Nesima, ARNAS Garibaldi Catania Italy 95100
    172 Azienda Ospedaliera "Istituti Ospitalieri" di Cremona Cremona Italy 26100
    173 AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can Genova Italy 16132
    174 Azienda Ospedaliera Fatebenefratelli e Oftalmico Milano Italy 20121
    175 Istituto Oncologico Veneto IOV-IRCCS Padova Italy 35128
    176 Ospedale Guglielmo da Saliceto, AUSL Piacenza Piacenza Italy 29100
    177 Unità di Biostatistica e Sperimentazioni Cliniche IRST Ravenna Italy 48100
    178 Ospedale Molinette, AO Città della Salute e della Scienza di Torino Italy 10126
    179 Aichi Cancer Center Hospital Nagoya Aichi Japan
    180 National Cancer Center Hospital East Kashiwa Chiba Japan
    181 National Hospital Organization Shikoku Cancer Center Matsuyama Ehime Japan
    182 Hokkaido University Hospital Sapporo Hokkaido Japan
    183 Kobe City Medical Center General Hospital Kobe Hyogo Japan
    184 Saku Central Hospital Advanced Care Center Saku Nagano Japan
    185 Osaka University Hospital Suita Osaka Japan
    186 Saitama Cancer Center Kita-Adachi Saitama Japan
    187 Shizuoka Cancer Center Sunto Shizuoka Japan
    188 Tochigi Cancer Center Utsunomiya Tochigi Japan
    189 National Cancer Center Hospital Chuo Tokyo Japan
    190 Kyorin University Hospial Mitaka Tokyo Japan
    191 Chiba Cancer Center Chiba Japan
    192 Gifu University Hospital Gifu Japan
    193 Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Japan
    194 Seoul National University Bundang Hospital SeongNam Gyeonggido Korea, Republic of 463-707
    195 Samsung Medical Center Seoul Seoul Teugbyeolsi Korea, Republic of 135-710
    196 Asan medical Center Seoul Seoul Teugbyeolsi Korea, Republic of 138-736
    197 Seoul National University Hospital Seoul Seoul Teugbyeolsi Korea, Republic of 138-736
    198 Hospital of Lithuanian University of Health sciences Kaunas Kauno Apskritis Lithuania LT-45434
    199 Hospital of Lithuanian University of Health Sciences Kaunas Kauno Apskritis Lithuania LT-50009
    200 Respublikine Panevezio ligonine Panevezys Panevežio Apskritis Lithuania LT-35144
    201 National Cancer Institute Vilnius Vilniaus Apskritis Lithuania LT-08860
    202 Klaipeda University Hospital Klaipeda Lithuania LT-92288
    203 Vilniaus Universiteto ligonines Santariskiu Klinikos Vilnius Lithuania LT-08661
    204 Siauliai County Hospital Siauliai Šiauliu Apskritis Lithuania LT-76231
    205 Centrum Onkologii im. F.Lukaszczyka Bydgoszcz Kujawsko-pomorskie Poland 85-796
    206 Szpital Specjalistyczny im. L. Rydygiera w Krakowie Krakow Malopolskie Poland 31-108
    207 Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina Otwock Mazowieckie Poland 05-400
    208 Centrum Onkologii Instytut im. M. Sklodowskiej-Curie Warszawa Mazowieckie Poland 02-781
    209 Magodent sp. z o.o. Szpital Onkologiczny Warszawa Mazowieckie Poland 03-291
    210 Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onko Brzozow Podkarpackie Poland 36-20
    211 Wojewodzkie Centrum Onkologii w Gdansku Gdansk Pomorskie Poland 80-210
    212 NZOZ Centrum Medyczne HCP Lecznictwo Stacjonarne Poznan Wielkopolskie Poland 61-485
    213 Zachodniopomorskie Centrum Onkologii Szczecin Zachodniopomorskie Poland 71-730
    214 Wojewodzki Szpital Specjalistyczny im. M.Kopernika Lodz Łódzkie Poland 93-510
    215 Radiotherapy Center CJ radioterapie si chimioterapie adulti Floresti Cluj Romania 407280
    216 Centrul de Oncologie Sf. Nectarie Craiova Dolj Romania 200347
    217 Oncolab Craiova Dolj Romania 200385
    218 Sp. Jud. de Urg. "Dr. Constantin Opris" Baia Mare Baia-Mare Maramures Romania 430031
    219 Oncomed Timisoara Timis Romania 300239
    220 Spitalul Clinic Municipal de Urgenta Timisoara Timisoara Timis Romania 300239
    221 Med Life Bucuresti Romania 010719
    222 Spitalul Clinic CF 2 Bucuresti Romania 011464
    223 Institutul Clinic Fundeni Bucuresti Romania 022328
    224 Centrul de Oncologie Euroclinic Iasi Romania 700106
    225 Institutul Regional de Oncologie Iasi Lasi Romania 700483
    226 Spitalul Clinic Judetean de Urgenta Sibiu Sibiu Romania 550245
    227 Republican Clinical Oncology Dispensary Ufa Bahkortostan, Respublika Russian Federation 450054
    228 Military Medical Academy n.a. S.M. Kirov Saint Petersburg Leningradskaya Oblast' Russian Federation 190121
    229 Russian Oncological Research Center n.a. N.N. Blokhin RAMS Moscow Moskva Russian Federation 115478
    230 City Clinical Hospital #40 Moscow Moskva Russian Federation 129301
    231 GUZ Perm Regional Oncology Dispensary Perm Permskiy Kray Russian Federation 614066
    232 Northwestern State Medical University n.a. Mechnikov Saint Petersburg Sankt-Peterburg Russian Federation 195067
    233 First Pavlov State Medical University of Saint-Petersburg Saint Petersburg Sankt-Peterburg Russian Federation 197022
    234 GBUZ Saint Petersburg clinical scientific and practical cent Saint Petersburg Sankt-Peterburg Russian Federation 197758
    235 SPb State Budget Institution Oncology Dispansery Saint Petersburg Sankt-Petersburg Russian Federation 198255
    236 GBUZ of Stavropol Territory Pyatigorsk Oncology Dispensary Pyatigorsk Stavropol'skiy Kray Russian Federation 357502
    237 Guz Clinical Oncology Dispensary #1 Krasnodar Russian Federation 350040
    238 H.U.V. Macarena Sevilla Andalucía Spain 41009
    239 Institut Català d'Oncologia-Hospital Germans Trias i Pujol Badalona Barcelona Spain 08916
    240 C.A.AV-H.Ntra.Sra.de Sonsoles Avila Castilla Y León Spain 05004
    241 H.U.P Hierro-Majadahonda Majadahonda Madrid Spain 28222
    242 H.del Mar Barcelona Spain 08003
    243 Hospital Universitario Vall d'Hebrón Barcelona Spain 08035
    244 H.Sta.Creu i St.Pau Barcelona Spain 08041
    245 H.U. de Burgos Burgos Spain 09006
    246 Institut Catalá d´Oncología (I.C.O.) Hospitalet de Llobregat Spain 08907
    247 H.G.U. G. Marañón Madrid Spain 28007
    248 M.D. Anderson Cancer Center Madrid Madrid Spain 28033
    249 H.U. R. y Cajal Madrid Spain 28034
    250 H.C. S.Carlos Madrid Spain 28040
    251 H.U.V.Arrixaca Murcia Spain 30120
    252 H.U.V. del Rocío Sevilla Spain 41013
    253 C.H.G.U.de Valencia Valencia Spain 46014
    254 H.U. Miguel Servet Zaragoza Spain 50009
    255 Aberdeen Royal Infirmary Aberdeen Aberdeen City United Kingdom AB25 2ZN
    256 The Beatson West Of Scotland Cancer Centre Glasgow Glasgow City United Kingdom G12 0YH
    257 Royal Surrey County Hospital Guildford Surrey United Kingdom GU2 7XX
    258 The Royal Marsden Hospital Sutton Surrey United Kingdom SM2 5PT
    259 The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital Sutton Surrey United Kingdom SM2 5PT
    260 Belfast City Hospital Belfast United Kingdom BT9 7AB
    261 St. Georges Hospital London United Kingdom SE1 2PR
    262 Christie Hospital NHS Foundation Trust Manchester United Kingdom M20 4BX
    263 Southampton University Hospital Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Sumitomo Pharma Oncology, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sumitomo Pharma Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02178956
    Other Study ID Numbers:
    • BBI608-336
    • 2014-000774-18
    First Posted:
    Jul 1, 2014
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details 714 patients were enrolled to this study from 02OCT2014 to 20SEP2017 across 204 sites in 22 countries.
    Pre-assignment Detail Study arm was determined at patient randomization to the study, no pre-assignment activities occurred.
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
    Period Title: Overall Study
    STARTED 357 357
    COMPLETED 286 279
    NOT COMPLETED 71 78

    Baseline Characteristics

    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel Total
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Total of all reporting groups
    Overall Participants 357 357 714
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.787
    (11.5130)
    59.887
    (11.1231)
    60.337
    (11.3207)
    Sex: Female, Male (Count of Participants)
    Female
    96
    26.9%
    103
    28.9%
    199
    27.9%
    Male
    261
    73.1%
    254
    71.1%
    515
    72.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.3%
    1
    0.1%
    Asian
    107
    30%
    102
    28.6%
    209
    29.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    0.6%
    3
    0.8%
    5
    0.7%
    White
    237
    66.4%
    240
    67.2%
    477
    66.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    11
    3.1%
    11
    3.1%
    22
    3.1%
    ECOG (Count of Participants)
    0: Fully active, able to carry on all pre-disease performance without restriction
    128
    35.9%
    134
    37.5%
    262
    36.7%
    1: Restricted in physically strenuous activity but ambulatory, can carry out light/sedentary work
    229
    64.1%
    223
    62.5%
    452
    63.3%
    BMI (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    23.24
    (4.481)
    23.56
    (4.709)
    23.40
    (4.596)

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description The primary objective of this study is to assess the effect of orally administered BBI608 plus weekly paclitaxel, in comparison to placebo plus weekly paclitaxel on the Overall Survival of patients with advanced histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma who failed treatment with one platinum/fluoropyrimidine containing regimen for unresectable or metastatic disease.
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
    Measure Participants 357 357
    Median (95% Confidence Interval) [Months]
    6.93
    7.36
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Napabucasin + Paclitaxel, Placebo + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8596
    Comments two-sided
    Method Log Rank
    Comments stratified log rank test stratified by region, time to progression on 1st line therapy and disease measurability.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.86 to 1.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR is for napabucasin + Paclitaxel vs Placebo + Paclitaxel. Based on Cox Proportional hazards model stratified by actual stratification variables including region, time to progression on first line therapy and disease measurability.
    2. Secondary Outcome
    Title Progression Free Survival
    Description Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause which comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in anon-target lesion, or the appearance of new lesions.
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
    Measure Participants 357 357
    Median (95% Confidence Interval) [Months]
    3.55
    3.68
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Napabucasin + Paclitaxel, Placebo + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9028
    Comments two sided
    Method Log Rank
    Comments stratified log rank test stratified by region, time to progression on 1st line therapy and disease measurability.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.85 to 1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR is for napabucuasin + Paclitaxel vs Placebo + Paclitaxel. Based on Cox Proportional hazards model stratified by actual stratification variables including region, time to progression on first line therapy and disease measurability.
    3. Secondary Outcome
    Title Objective Response Rate
    Description Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients were included in this group had a baseline scan and at least one assessment a minimum of 6 weeks from baseline. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients were included in this group had a baseline scan and at least one assessment a minimum of 6 weeks from baseline.
    Measure Participants 289 283
    Count of Participants [Participants]
    16
    4.5%
    18
    5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Napabucasin + Paclitaxel, Placebo + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7359
    Comments 2-sided
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by actual stratification variables at baseline including region, and time to progression on first-line therapy.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.60 to 1.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio for napabucasin vs. Placebo. Based on Logistic Regression Model adjusting for actual Stratification variables at baseline including region, and time to progression on first-line therapy.
    4. Secondary Outcome
    Title Disease Control Rate
    Description Disease control Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR+SD) based on RECIST 1.1.
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients were included in this group had a baseline scan and at least one assessment a minimum of 6 weeks from baseline. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients were included in this group had a baseline scan and at least one assessment a minimum of 6 weeks from baseline.
    Measure Participants 289 283
    Count of Participants [Participants]
    55
    15.4%
    58
    16.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Napabucasin + Paclitaxel, Placebo + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6555
    Comments 2-sided
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by actual stratification variables at baseline including region, and time to progression on first-line therapy.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.66 to 1.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio for napabucasin vs. Placebo. Based on Logistic Regression Model adjusting for actual Stratification variables at baseline including region, and time to progression on first-line therapy.
    5. Secondary Outcome
    Title Number of Patients With Adverse Events
    Description All patients who have received at least one dose of BBI608/Placebo will be included in the safety analysis. The number of patients who experienced at least one adverse event is reported.
    Time Frame 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients included this group received at least one dose of study drug. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Patients included this group received at least one dose of study drug.
    Measure Participants 357 350
    Count of Participants [Participants]
    352
    98.6%
    338
    94.7%

    Adverse Events

    Time Frame Adverse Events were collected from the time the patient signed informed consent until 30 days after the last protocol treatment administration.
    Adverse Event Reporting Description
    Arm/Group Title Napabucasin + Paclitaxel Placebo + Paclitaxel
    Arm/Group Description Napabucasin was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Napabucasin administration began 2 days prior to the first paclitaxel infusion in the initial run in period. Placebo was administered orally, twice daily, with doses separated by 12 hours. Paclitaxel 80 mg/m2 (intravenous [IV]) was administered weekly, on Days 1, 8, and 15 of each 28 day study cycle. Placebo administration began 2 days prior to the first paclitaxel infusion in the initial run in period.
    All Cause Mortality
    Napabucasin + Paclitaxel Placebo + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 286/357 (80.1%) 275/350 (78.6%)
    Serious Adverse Events
    Napabucasin + Paclitaxel Placebo + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 125/357 (35%) 101/350 (28.9%)
    Blood and lymphatic system disorders
    Anaemia 6/357 (1.7%) 5/350 (1.4%)
    Agranulocytosis 0/357 (0%) 1/350 (0.3%)
    Febrile neutropenia 1/357 (0.3%) 2/350 (0.6%)
    Bone marrow 2/357 (0.6%) 0/350 (0%)
    Microangiopathic haemolytic anaemia 0/357 (0%) 1/350 (0.3%)
    Neutropenia 0/357 (0%) 1/350 (0.3%)
    Cardiac disorders
    Acute myocardial infarction 1/357 (0.3%) 0/350 (0%)
    Angina unstable 1/357 (0.3%) 0/350 (0%)
    Atrial fibrillation 4/357 (1.1%) 1/350 (0.3%)
    Myocardial infarction 0/357 (0%) 1/350 (0.3%)
    Bradycardia 1/357 (0.3%) 0/350 (0%)
    Palpitations 1/357 (0.3%) 0/350 (0%)
    Gastrointestinal disorders
    Vomiting 14/357 (3.9%) 2/350 (0.6%)
    Nausea 6/357 (1.7%) 0/350 (0%)
    Abdominal Pain 8/357 (2.2%) 5/350 (1.4%)
    Diarrhoea 10/357 (2.8%) 3/350 (0.9%)
    Abdominal pain upper 4/357 (1.1%) 1/350 (0.3%)
    Gastric haemorrhage 4/357 (1.1%) 3/350 (0.9%)
    Intestinal obstruction 5/357 (1.4%) 3/350 (0.9%)
    Ascites 3/357 (0.8%) 3/350 (0.9%)
    Dysphagia 3/357 (0.8%) 5/350 (1.4%)
    Upper gastrointestinal haemorrhage 3/357 (0.8%) 2/350 (0.6%)
    Abdominal distension 2/357 (0.6%) 1/350 (0.3%)
    Colitis 2/357 (0.6%) 0/350 (0%)
    Gastritis 2/357 (0.6%) 0/350 (0%)
    Gastrointestinal haemorrhage 2/357 (0.6%) 1/350 (0.3%)
    Ileus 2/357 (0.6%) 3/350 (0.9%)
    Small intestinal obstruction 2/357 (0.6%) 4/350 (1.1%)
    Abdominal pain lower 1/357 (0.3%) 0/350 (0%)
    Gastric perforation 1/357 (0.3%) 0/350 (0%)
    Gastric stenosis 1/357 (0.3%) 1/350 (0.3%)
    Gastrooesophageal reflux disease 1/357 (0.3%) 0/350 (0%)
    Haematemesis 1/357 (0.3%) 3/350 (0.9%)
    Intra-abdominal haemorrhage 1/357 (0.3%) 0/350 (0%)
    Jejunal stenosis 1/357 (0.3%) 0/350 (0%)
    Large intestine obstruction 1/357 (0.3%) 0/350 (0%)
    Large intestine perforation 1/357 (0.3%) 0/350 (0%)
    Mechanical ileus 1/357 (0.3%) 0/350 (0%)
    Oesophageal haemorrhage 1/357 (0.3%) 0/350 (0%)
    Oesophagitis 1/357 (0.3%) 0/350 (0%)
    Constipation 0/357 (0%) 1/350 (0.3%)
    Gastrointestinal obstruction 0/357 (0%) 1/350 (0.3%)
    Subileus 1/357 (0.3%) 0/350 (0%)
    Oesophageal obstruction 0/357 (0%) 1/350 (0.3%)
    General disorders
    Fatigue 5/357 (1.4%) 0/350 (0%)
    Pyrexia 6/357 (1.7%) 6/350 (1.7%)
    Adverse event 1/357 (0.3%) 0/350 (0%)
    General physical health deterioration 3/357 (0.8%) 1/350 (0.3%)
    Asthenia 4/357 (1.1%) 3/350 (0.9%)
    Death 0/357 (0%) 3/350 (0.9%)
    Hyperthermia 0/357 (0%) 1/350 (0.3%)
    Stent malfunction 0/357 (0%) 1/350 (0.3%)
    Hepatobiliary disorders
    Sudden death 1/357 (0.3%) 0/350 (0%)
    Bile duct obstruction 1/357 (0.3%) 1/350 (0.3%)
    Cholangitis 1/357 (0.3%) 1/350 (0.3%)
    Cholecystitis acute 1/357 (0.3%) 0/350 (0%)
    Hepatic failure 1/357 (0.3%) 0/350 (0%)
    Hypertransaminasaemia 0/357 (0%) 1/350 (0.3%)
    Immune system disorders
    Anaphylactic reaction 0/357 (0%) 1/350 (0.3%)
    Hypersensitivity 0/357 (0%) 1/350 (0.3%)
    Drug hypersensitivity 1/357 (0.3%) 0/350 (0%)
    Infections and infestations
    Pneumonia 5/357 (1.4%) 4/350 (1.1%)
    Respiratory tract infection 3/357 (0.8%) 0/350 (0%)
    Urinary tract infection 3/357 (0.8%) 2/350 (0.6%)
    Lung infection 4/357 (1.1%) 3/350 (0.9%)
    Peritonitis 2/357 (0.6%) 1/350 (0.3%)
    Sepsis 2/357 (0.6%) 1/350 (0.3%)
    Septic shock 2/357 (0.6%) 1/350 (0.3%)
    Abdominal infection 1/357 (0.3%) 1/350 (0.3%)
    Bronchitis 1/357 (0.3%) 0/350 (0%)
    Bronchopneumonia 1/357 (0.3%) 0/350 (0%)
    Clostridium difficile colitis 1/357 (0.3%) 0/350 (0%)
    Diverticulitis 1/357 (0.3%) 0/350 (0%)
    Gastrointestinal infection 1/357 (0.3%) 0/350 (0%)
    Infection 0/357 (0%) 2/350 (0.6%)
    Herpes zoster 1/357 (0.3%) 0/350 (0%)
    Pyonephrosis 1/357 (0.3%) 0/350 (0%)
    Localised infection 0/357 (0%) 1/350 (0.3%)
    Pharyngitis 0/357 (0%) 1/350 (0.3%)
    Upper respiratory tract infection 0/357 (0%) 2/350 (0.6%)
    Injury, poisoning and procedural complications
    Fall 0/357 (0%) 1/350 (0.3%)
    Femur fracture 1/357 (0.3%) 0/350 (0%)
    Investigations
    Neutrophil count decreased 2/357 (0.6%) 0/350 (0%)
    Blood creatinine increased 1/357 (0.3%) 0/350 (0%)
    General physical condition abnormal 1/357 (0.3%) 0/350 (0%)
    White blood cell count decreased 1/357 (0.3%) 1/350 (0.3%)
    Alanine aminotransferase increased 0/357 (0%) 1/350 (0.3%)
    Aspartate aminotransferase increased 0/357 (0%) 1/350 (0.3%)
    Blood bilirubin increased 0/357 (0%) 2/350 (0.6%)
    Blood creatine phosphokinase increased 0/357 (0%) 1/350 (0.3%)
    Blood urea increased 0/357 (0%) 1/350 (0.3%)
    Liver function test abnormal 0/357 (0%) 1/350 (0.3%)
    Platelet count decreased 0/357 (0%) 1/350 (0.3%)
    Transaminases increased 0/357 (0%) 1/350 (0.3%)
    Metabolism and nutrition disorders
    Decreased appetite 5/357 (1.4%) 2/350 (0.6%)
    Fluid retention 1/357 (0.3%) 0/350 (0%)
    Hypokalaemia 2/357 (0.6%) 0/350 (0%)
    Dehydration 5/357 (1.4%) 1/350 (0.3%)
    Hypoglycaemia 0/357 (0%) 1/350 (0.3%)
    Hyponatraemia 0/357 (0%) 2/350 (0.6%)
    Musculoskeletal and connective tissue disorders
    Bone pain 0/357 (0%) 1/350 (0.3%)
    Muscular weakness 1/357 (0.3%) 0/350 (0%)
    Back pain 2/357 (0.6%) 3/350 (0.9%)
    Flank pain 0/357 (0%) 1/350 (0.3%)
    Spinal osteoarthritis 0/357 (0%) 1/350 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gastric cancer 0/357 (0%) 1/350 (0.3%)
    Metastases to meninges 0/357 (0%) 1/350 (0.3%)
    Tumour haemorrhage 0/357 (0%) 1/350 (0.3%)
    Tumour pain 0/357 (0%) 1/350 (0.3%)
    Nervous system disorders
    Cerebral infarction 1/357 (0.3%) 0/350 (0%)
    Cerebrovascular accident 3/357 (0.8%) 0/350 (0%)
    Brain oedema 0/357 (0%) 1/350 (0.3%)
    Headache 1/357 (0.3%) 0/350 (0%)
    Syncope 1/357 (0.3%) 0/350 (0%)
    Neuralgia 0/357 (0%) 1/350 (0.3%)
    Psychiatric disorders
    Confusional state 0/357 (0%) 1/350 (0.3%)
    Renal and urinary disorders
    Renal failure acute 3/357 (0.8%) 1/350 (0.3%)
    Nephrolithiasis 1/357 (0.3%) 1/350 (0.3%)
    Renal failure 1/357 (0.3%) 0/350 (0%)
    Urinary retention 1/357 (0.3%) 0/350 (0%)
    Renal injury 0/357 (0%) 1/350 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 3/357 (0.8%) 7/350 (2%)
    Aspiration 1/357 (0.3%) 0/350 (0%)
    Pleural effusion 1/357 (0.3%) 0/350 (0%)
    Pneumonia aspiration 1/357 (0.3%) 1/350 (0.3%)
    Cough 0/357 (0%) 1/350 (0.3%)
    Laryngeal obstruction 0/357 (0%) 1/350 (0.3%)
    Pulmonary embolism 1/357 (0.3%) 2/350 (0.6%)
    Pneumonitis 0/357 (0%) 3/350 (0.9%)
    Vascular disorders
    Circulatory collapse 1/357 (0.3%) 0/350 (0%)
    Embolism 2/357 (0.6%) 0/350 (0%)
    Hypotension 2/357 (0.6%) 0/350 (0%)
    Haemorrhage 1/357 (0.3%) 0/350 (0%)
    Peripheral artery thrombosis 1/357 (0.3%) 0/350 (0%)
    Thrombosis 1/357 (0.3%) 0/350 (0%)
    Venous thrombosis 1/357 (0.3%) 0/350 (0%)
    Other (Not Including Serious) Adverse Events
    Napabucasin + Paclitaxel Placebo + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 352/357 (98.6%) 338/350 (96.6%)
    Blood and lymphatic system disorders
    Anaemia 126/357 (35.3%) 118/350 (33.7%)
    Neutropenia 37/357 (10.4%) 49/350 (14%)
    Leukopenia 22/357 (6.2%) 19/350 (5.4%)
    Gastrointestinal disorders
    Diarrhoea 304/357 (85.2%) 126/350 (36%)
    Nausea 178/357 (49.9%) 123/350 (35.1%)
    Abdominal pain 140/357 (39.2%) 93/350 (26.6%)
    Vomiting 135/357 (37.8%) 95/350 (27.1%)
    Constipation 61/357 (17.1%) 78/350 (22.3%)
    Abdominal pain upper 35/357 (9.8%) 40/350 (11.4%)
    Abdominal distension 28/357 (7.8%) 25/350 (7.1%)
    Dysphagia 22/357 (6.2%) 24/350 (6.9%)
    Ascites 18/357 (5%) 17/350 (4.9%)
    General disorders
    Fatigue 110/357 (30.8%) 92/350 (26.3%)
    Asthenia 73/357 (20.4%) 73/350 (20.9%)
    Pyrexia 57/357 (16%) 40/350 (11.4%)
    Oedema peripheral 38/357 (10.6%) 31/350 (8.9%)
    Infections and infestations
    Urinary tract infection 29/357 (8.1%) 12/350 (3.4%)
    Investigations
    Neutrophil count decreased 48/357 (13.4%) 53/350 (15.1%)
    Weight decreased 41/357 (11.5%) 23/350 (6.6%)
    White blood cell count decreased 35/357 (9.8%) 43/350 (12.3%)
    Metabolism and nutrition disorders
    Decreased appetite 129/357 (36.1%) 103/350 (29.4%)
    Hypokalaemia 29/357 (8.1%) 9/350 (2.6%)
    Hypoalbuminaemia 20/357 (5.6%) 18/350 (5.1%)
    Musculoskeletal and connective tissue disorders
    Back pain 31/357 (8.7%) 33/350 (9.4%)
    Arthralgia 17/357 (4.8%) 28/350 (8%)
    Nervous system disorders
    Neuropathy peripheral 46/357 (12.9%) 38/350 (10.9%)
    Peripheral sensory neuropathy 37/357 (10.4%) 47/350 (13.4%)
    Dysgeusia 27/357 (7.6%) 15/350 (4.3%)
    Dizziness 19/357 (5.3%) 19/350 (5.4%)
    Paraesthesia 17/357 (4.8%) 22/350 (6.3%)
    Psychiatric disorders
    Insomnia 30/357 (8.4%) 27/350 (7.7%)
    Renal and urinary disorders
    Chromaturia 47/357 (13.2%) 3/350 (0.9%)
    Respiratory, thoracic and mediastinal disorders
    Cough 35/357 (9.8%) 34/350 (9.7%)
    Dyspnoea 30/357 (8.4%) 37/350 (10.6%)
    Skin and subcutaneous tissue disorders
    Alopecia 73/357 (20.4%) 94/350 (26.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Marilyn Fontaine
    Organization Sumitomo Dainippon Pharma Oncology
    Phone 617-674-8556
    Email mfontaine@bostonbiomedical.com
    Responsible Party:
    Sumitomo Pharma Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02178956
    Other Study ID Numbers:
    • BBI608-336
    • 2014-000774-18
    First Posted:
    Jul 1, 2014
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022