Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer
- Conditions
- Cervical Cancer
- Interventions
- Registration Number
- NCT04697628
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent).
Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of five different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, pemetrexed, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 502
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tisotumab vedotin tisotumab vedotin Tisotumab vedotin monotherapy Chemotherapy topotecan Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) Chemotherapy vinorelbine Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) Chemotherapy gemcitabine Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) Chemotherapy irinotecan Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) Chemotherapy pemetrexed Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
- Primary Outcome Measures
Name Time Method Overall Survival From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months) Overall survival is defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) as Assessed by Investigator From the date of randomization to first documentation of PD or death due to any cause, or censoring date whichever occurred first (maximum up to 25 months) PFS per investigator was defined as the time from the date of randomization to the first documentation of disease progression (PD) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, or death due to any cause, whichever occurred earlier. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Participants without evidence of radiographic disease progression or death were censored at the date of last adequate tumor assessment prior to data cut-off date or start of new anti-cancer therapy. Participants with disease progression or death that occurred after 2 or more missed scans were censored at the last adequate tumor assessment prior to missed scans. Participants without post-baseline scan data were censored at the day of randomization.
EQ-5D Visual Analog Scale (VAS) Scores From start of treatment until end of follow-up EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state) ; higher scores indicate a better health state.
Confirmed Objective Response Rate (ORR) as Assessed by Investigator From the date of randomization until date of confirmed CR or PR (maximum up to 25 months) Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The minimum criteria for stable disease (SD) duration are defined as ≥ 5 weeks after the date of randomization. For a response to be considered as confirmed, the subsequent response had to be at least 4 weeks after the initial response. Two-sided 95% exact confidence interval (CI) was computed using the Clopper-Pearson method.
Duration of Response (DOR) by Investigator Assessment From the date of first documented response of CR or PR to the first documented PD or death from any cause, whichever occurred first (maximum up to 25 months) DOR was defined as the time from the date of the first confirmed objective response (CR or PR that was subsequently confirmed) to the date of the first documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score From start of treatment until end of follow-up The EQ-5D-5L questionnaire is a 5-item self-reported measure of functioning and well-being, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems and extreme problems). Responses to the 5 items are then converted to a weighted health state index (utility score) based on values derived from general population samples. This health utility score is between 0 and 1, where 0 is death and 1 is perfect health.
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score From start of treatment until end of follow-up The EORTC-QLQ-C30 questionnaire is composed of 30 questions for which the answers ranges either from 1 (not at all) to 4 (very much) for items 1 to 28, or from 1 (very poor) to 7 (excellent) for items 29 to 30. The EORTC QLQ-C30 scale scores will be calculated using the EORTC QLQ-C30 Scoring Manual. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items (i.e., no item occurs in more than one scale). All of the scales and single-item measures range in score from 0 to 100, with a high scale score representing a higher response level (e.g., a high level of functioning, a high QoL, or a high level of symptomatology/problems)
EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores From start of treatment until end of follow-up The EORTC QLQ-CX24 questionnaire is meant for use among cervical cancer participants varying in disease stage and treatment modality. The EORTC-QLQ-CX24 questionnaire is composed of 24 questions for which the answers ranged from 1 (Not at all) to 4 (Very much). Four functional scales and 5 symptom scales will be calculated using the EORTC QLQ-CX24 Scoring Manual. The 9 scores computed from the EORTC-QLQ-CX24 questionnaire will be summarized by treatment arm using descriptive statistics.
Time-to-Response (TTR) as Assessed by the Investigator From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months) TTR was defined as the time from the randomization date to the date of the first confirmed objective response (CR or PR that was subsequently confirmed). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) From start of treatment up to 30 days after last dose of study treatment (up to 25 months) An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment and with onset date on or before 30 days after the last dose of study treatment.
Trial Locations
- Locations (192)
Willis-Knighton Physician Network/Gynecologic Oncology Associates
🇺🇸Shreveport, Louisiana, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
Fondazione Policlinico Universitario Agostino
🇮🇹Roma, Other, Italy
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Other, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou City, Other, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou City, Other, China
Shanxi Province Cancer Hospital
🇨🇳Taiyuan, Other, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, Other, China
Instituto Alexander Fleming
🇦🇷Caba, Argentina
Fakultni nemocnice Brno
🇨🇿Brno-stred-Veveri, Other, Czechia
Jilin University - First Affiliated Hospital - Cancer Center
🇨🇳Changchun, Other, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, Other, China
Sichuan Cancer Hospital
🇨🇳Chengdu, Other, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Other, China
General University Hospital Prague
🇨🇿Praha 2, Other, Czechia
St. Dominic - Jackson Memorial Hospital
🇺🇸Jackson, Mississippi, United States
Hunan Cancer Hospital
🇨🇳Changsha, Other, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, Other, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Other, China
Hubei Cancer Hospital
🇨🇳Wuhan, Other, China
Beijing Obstetrics and Gynecology Hospital
🇨🇳Beijing, Other, China
Peking University People's Hospital
🇨🇳Beijing, Other, China
The Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, Other, China
Shandong Cancer Hospital
🇨🇳Jinan, Other, China
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika
🇨🇿Olomouc, Other, Czechia
Hospital Na Bulovce
🇨🇿Praha 8-Liben, Other, Czechia
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Other, Korea, Republic of
Hospital Clinic de Barcelona
🇪🇸Barcelona, Other, Spain
Hyogo Cancer Center
🇯🇵Akashi, Japan
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan City, Other, China
Guangxi Medical University Affiliated Tumor Hospital
🇨🇳Nanning, China
Amsterdam UMC, Locatie AMC
🇳🇱Amsterdam, Other, Netherlands
Weill Cornell Medicine
🇺🇸Flushing, New York, United States
University of California Irvine Medical Center
🇺🇸Irvine, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Gynecological Cancer Institute of Chicago, LLC
🇺🇸Oak Lawn, Illinois, United States
New York University (NYU) Cancer Institute
🇺🇸New York, New York, United States
Cleveland Clinic Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic, The
🇺🇸Cleveland, Ohio, United States
Kettering Health
🇺🇸Kettering, Ohio, United States
Ohio State University Clinical Trials Management Office
🇺🇸Hilliard, Ohio, United States
Cleveland Clinic Hillcrest Hospital
🇺🇸Mayfield Heights, Ohio, United States
Texas Oncology - Fort Worth 12th Avenue
🇺🇸Fort Worth, Texas, United States
Texas Oncology - The Woodlands
🇺🇸The Woodlands, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
AKH - Medizinische Universitat Wien
🇦🇹Vienna, Other, Austria
Hospital Mãe de Deus
🇧🇷Porto Alegre, Other, Brazil
Hospital Beneficencia Portuguesa
🇧🇷Sao Paulo, Other, Brazil
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Instituto Oncologico de Cordoba
🇦🇷Córdoba, Other, Argentina
Sanatorio de la Mujer
🇦🇷Rosario, Argentina
LKH- Universitat Klinikum Graz
🇦🇹Graz, Other, Austria
Institut Jules Bordet
🇧🇪Anderlecht, Other, Belgium
UZ Leuven campus Gasthuisberg
🇧🇪Leuven, Other, Belgium
CHU de Liege
🇧🇪Liege, Other, Belgium
CHU UCL Namur-Site de Saint Elisabeth
🇧🇪Namur, Other, Belgium
Centro de Pesquisa em Oncologia - HSL-PUCRS
🇧🇷Porto Alegre, Other, Brazil
Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie
🇫🇷Bordeaux, Other, France
Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Avron (Hopital de la Croix Saint-Simon)
🇫🇷Paris, Other, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, Other, France
Universitaetsklinikum Essen
🇩🇪Essen, Other, Germany
Azienda Ospedaliera per l'Emergenza
🇮🇹Catania, Other, Italy
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
National Institute of Oncology Hungary
🇭🇺Budapest, Pest, Other, Hungary
Hospital San Bortolo
🇮🇹Vicenza, Other, Italy
National Cancer Center Hospital
🇯🇵Chuo-ku, Other, Japan
Kurume University Hospital
🇯🇵Fukuoka, Other, Japan
Gunma University Hospital
🇯🇵Gunma, Other, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Other, Japan
Nippon Medical School Musashi Kosugi Hospital
🇯🇵Kawasaki, Other, Japan
Augusta University
🇺🇸Augusta, Georgia, United States
ZNA Middelheim
🇧🇪Antwerpen, Other, Belgium
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Hospital de Caridade de Ijui
🇧🇷Ijui, Other, Brazil
Fundacao Antonio Prudente (AC Camargo Cancer Center)
🇧🇷Sao Paulo, Other, Brazil
Carbone Cancer Center / University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Fundacion Cenit
🇦🇷Caba, Argentina
Universitair Ziekenhuis Gent
🇧🇪Gent, Other, Belgium
Brazilian National Cancer Institute
🇧🇷Rio de Janeiro, Other, Brazil
CARIO - Centre Armoricain De Radiothérapie, D'imagerie Médicale Et D'oncologie
🇫🇷Cotes d'Armor, Other, France
Universitaetsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Other, Germany
University Hospital LMU Munich
🇩🇪Munchen, Other, Germany
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
🇮🇹Meldola, Italy
Okayama University Hospital
🇯🇵Okayama, Other, Japan
Jikei University Hospital
🇯🇵Tokyo, Other, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Other, Japan
Soon Chun Hyang University Hospital Seoul
🇰🇷Seoul, Other, Korea, Republic of
Radboud University Medical Center
🇳🇱Nijmegen, Other, Netherlands
Erasmus Medisch Centrum Daniel Den Hoed
🇳🇱Rotterdam, Other, Netherlands
Oslo University Hospital, Radiumhospitalet
🇳🇴Olso, Other, Norway
Oncology Associates of Oregon
🇺🇸Eugene, Oregon, United States
Instituto Brasileiro de Controle do Cancer
🇧🇷Formosa, Brazil
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Kuopio University Hospital
🇫🇮Kuopio, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Centre de Lutte contre le Cancer - Francois Baclesse
🇫🇷Caen Cedex 5, Other, France
Hopital Prive du Confluent
🇫🇷Nantes Cedex 2, Other, France
Institut Claudius Regaud IUCT-O
🇫🇷Toulouse Cedex 9, Other, France
University Hospital Waterford
🇮🇪Waterford, Other, Ireland
Kagoshima City Hospital
🇯🇵Kagoshima-City, Other, Japan
NHO Shikoku Cancer Center
🇯🇵Matsuyama, Other, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Other, Japan
Iwate Medical University Hospital
🇯🇵Shiwa-gun, Other, Japan
Ehime University Hospital
🇯🇵Ehime, Japan
CHA Bundang Medical Center
🇰🇷Seongnam, Other, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Other, Korea, Republic of
Institut de cancerologie Strasbourg Europe
🇫🇷Strasbourg, Other, France
University of Turku
🇫🇮Turku, Other, Finland
Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz
🇫🇷Besancon Cedex, Other, France
Institute Cancer De Lorraine (ICL) - Alexis Vautrin
🇫🇷Moselle, Other, France
Kliniken Essen-Mitte
🇩🇪Essen, Other, Germany
Medical and Health Science Centre Debrecen Institution of Internal Medicine
🇭🇺Debrecen, Hajdú-Bihar, Other, Hungary
Ospedale San Raffaele
🇮🇹Milano, Other, Italy
National Hospital Organization Kure Medical Center and Chugoku Cancer Center
🇯🇵Hiroshima, Other, Japan
The Jikei University Kashiwa Hospital
🇯🇵Kashiwashi, Other, Japan
Aichi Cancer Center
🇯🇵Nagoya-shi, Other, Japan
University of the Ryukyus Hospital
🇯🇵Nakagami-gun, Other, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Other, Japan
Keio University Hospital
🇯🇵Tokyo, Other, Japan
Korea Cancer Center Hospital
🇰🇷Seoul, Other, Korea, Republic of
National University Cancer Institute, Singapore
🇸🇬Singapore, Other, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Other, Singapore
Kanagawa Cancer Center
🇯🇵Yokohama, Other, Japan
Saitama Cancer Center
🇯🇵Hidaka-City, Other, Japan
Kagoshima University Hospital
🇯🇵Kagoshima City, Other, Japan
Kindai University Hospital
🇯🇵Osakasayama, Other, Japan
Shizuoka Cancer Center
🇯🇵Sunto-Gun, Other, Japan
National Cancer Center
🇰🇷Goyang-si, Other, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Other, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Other, Korea, Republic of
Inje University Busan-Paik Hospital
🇰🇷Busan, Korea, Republic of
Białostockie Centrum Onkologii
🇵🇱Białystok, Other, Poland
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo-shi, Other, Japan
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Other, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Other, Korea, Republic of
Yokohama City University Hospital
🇯🇵Yokohama, Other, Japan
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Sungkyunkwan University of Medicine - Samsung Changwon Hospital
🇰🇷Changwon, Kyungsangnam-do, Korea, Republic of
Oncologico Potosino
🇲🇽San Luis Potosi, Other, Mexico
Maastricht University Medical Center
🇳🇱Maastricht, Other, Netherlands
Trondheim University Hospital, Trondheim
🇳🇴Trondheim, Norway
Olive View - UCLA Medical Center
🇺🇸Sylmar, California, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Other, Belgium
Erasto Gaertner Hospital
🇧🇷Curitiba, Other, Brazil
Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Shanghai First People's Hospital
🇨🇳Shanghai, Other, China
The Affiliated Cancer Hospital of XinJiang Medical University
🇨🇳Urumqi, Other, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Other, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Other, China
Shaanxi Provincial People's Hospital
🇨🇳Xi'an, Other, China
The Second People's Hospital of Yibin
🇨🇳Yibin, Other, China
Rigshospitalet
🇩🇰Kobenhavn, Other, Denmark
Bacs-Kiskun Varmegyei Oktatokorhaz
🇭🇺Kecskemet, Other, Hungary
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Other, Korea, Republic of
Seoul Saint Mary's Hospital
🇰🇷Seoul, Other, Korea, Republic of
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Other, Netherlands
Hospital Maria Auxiliadora
🇵🇪Lima, Peru
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Other, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Other, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Other, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Other, Spain
Uppsala University Hospital (Akademiska Sjukhuset)
🇸🇪Uppsala, Other, Sweden
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Other, Spain
Linkoping University Hospital
🇸🇪Linköping, Other, Sweden
Skanes University Hospital - Universitetssjukhus
🇸🇪Lund, Other, Sweden
Taipei Veterans General Hospital
🇨🇳Taipei City, Other, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei City, Other, Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan, Other, Taiwan
Royal Devon and Exeter NHS Foundation Trust
🇬🇧Exeter, Other, United Kingdom
The Royal Marsden Hospital
🇬🇧London, Other, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, Other, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, Other, United Kingdom
The Royal Marsden Hospital (Surrey)
🇬🇧Sutton, Other, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associates, PC - HAL
🇺🇸Phoenix, Arizona, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Northwest Cancer Specialists, P.C.
🇺🇸Portland, Oregon, United States
Minnesota Oncology Hematology P.A.
🇺🇸Minneapolis, Minnesota, United States
Texas Oncology - Austin Central
🇺🇸Austin, Texas, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
University of Alberta / Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada