BRIGHTER: A Study of BBI608 Plus Weekly Paclitaxel to Treat Gastric and Gastro-Esophageal Junction Cancer
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 |
---|---|---|
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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
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: BBI608 plus Paclitaxel
|
Drug: BBI608
BBI608 480 mg orally two times daily (960 mg total daily dose)
Other Names:
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
- 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
- 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.
- 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.
- 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.
- 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
Inclusion Criteria:
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Cytologically or histologically confirmed advanced gastric or GEJ adenocarcinoma that is metastatic or locally advanced and unresectable.
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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.
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Paclitaxel therapy is appropriate for the patient and is recommended by the Investigator.
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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.
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
・≥ 18 years of age.
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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.
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Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.
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Alanine transaminase (ALT) ≤ 3 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases] within 14 days prior to randomization.
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Hemoglobin (Hgb) ≥ 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion within 1 week of baseline Hgb assessment.
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Total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
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Creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min (as calculated by the Cockroft-Gault equation) within 14 days prior to randomization.
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Absolute neutrophil count ≥ 1.5 x 10^9/L within 14 days prior to randomization.
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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.
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Other baseline laboratory evaluations must be done within 14 days prior to randomization.
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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.
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Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
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Patients must be accessible for treatment and follow up.
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Protocol treatment is to begin within 2 working days of patient randomization.
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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:
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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.
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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.
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More than one prior chemotherapy regimen administered in the metastatic setting.
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Major surgery within 4 weeks prior to randomization.
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Any known symptomatic brain metastases requiring steroids.
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Women who are pregnant or breastfeeding.
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Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent.
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Unable or unwilling to swallow BBI608/placebo capsules daily.
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Uncontrolled intercurrent illness.
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Peripheral neuropathy ≥ CTCAE Grade 2 at baseline.
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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.
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Prior treatment with BBI608.
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Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
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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 | |
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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.- BBI608-336
- 2014-000774-18
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
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. |
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. |
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. |
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. |
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
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 |
mfontaine@bostonbiomedical.com |
- BBI608-336
- 2014-000774-18