Clinical trial NCT04697628: Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer
Official title: A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs Investigator's Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cervical Cancer
Keywords: Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genmab
First posted: 2021-01-06
Enrollment: 502
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

* Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
* Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either:

  * paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or
  * paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or
  * paclitaxel + topotecan/nogitecan + bevacizumab + anti-PD-(L)1 agent
* Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the participant was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required.
* Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC cancer should be counted.
* Measurable disease according to RECIST v1.1 as assessed by the investigator.
* Has ECOG performance status of 0 or 1 prior to randomization.
* Has life expectancy of at least 3 months.

Exclusion Criteria

* Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned as part of the inclusion criteria above.
* Has clinically significant bleeding issues or risks. This includes known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry.
* Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack \>1 month prior to screening is allowed).
* Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and participants with penetrating ocular transplants. Cataracts alone is not an exclusion criterion.
* Major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration.
* Peripheral neuropathy ≥grade 2.
* Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs.

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months)
Secondary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Investigator
timeFrame: 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)
measure: Confirmed Objective Response Rate (ORR) as Assessed by Investigator
timeFrame: From the date of randomization until date of confirmed CR or PR (maximum up to 25 months)
measure: Time-to-Response (TTR) as Assessed by the Investigator
timeFrame: From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months)
measure: Duration of Response (DOR) by Investigator Assessment
timeFrame: 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)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From start of treatment up to 30 days after last dose of study treatment (up to 25 months)
measure: EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score
timeFrame: From start of treatment until end of follow-up
measure: EQ-5D Visual Analog Scale (VAS) Scores
timeFrame: From start of treatment until end of follow-up
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score
timeFrame: From start of treatment until end of follow-up
measure: EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores
timeFrame: From start of treatment until end of follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine Medical Center
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Oak Lawn
country: United States
facility: Gynecological Cancer Institute of Chicago, LLC
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Shreveport
country: United States
facility: Willis-Knighton Physician Network/Gynecologic Oncology Associates
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology P.A.
state: Minnesota
city: Jackson
country: United States
facility: St. Dominic - Jackson Memorial Hospital
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Brooklyn
country: United States
facility: Weill Cornell Medicine
state: New York
city: Flushing
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: New York University (NYU) Cancer Institute
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, The
state: Ohio
city: Hilliard
country: United States
facility: Ohio State University Clinical Trials Management Office
state: Ohio
city: Kettering
country: United States
facility: Kettering Health
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clinic Hillcrest Hospital
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Austin
country: United States
facility: Texas Oncology - Austin Central
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth 12th Avenue
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology - The Woodlands
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Córdoba
country: Argentina
facility: Instituto Oncologico de Cordoba
state: Other
city: Caba
country: Argentina
facility: Fundacion Cenit
city: Caba
country: Argentina
facility: Instituto Alexander Fleming
city: Rosario
country: Argentina
facility: Sanatorio de la Mujer
city: Graz
country: Austria
facility: LKH- Universitat Klinikum Graz
state: Other
city: Vienna
country: Austria
facility: AKH - Medizinische Universitat Wien
state: Other
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Other
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
state: Other
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
state: Other
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Other
city: Leuven
country: Belgium
facility: UZ Leuven campus Gasthuisberg
state: Other
city: Liege
country: Belgium
facility: CHU de Liege
state: Other
city: Namur
country: Belgium
facility: CHU UCL Namur-Site de Saint Elisabeth
state: Other
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Curitiba
country: Brazil
facility: Erasto Gaertner Hospital
state: Other
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui
state: Other
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus
state: Other
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa em Oncologia - HSL-PUCRS
state: Other
city: Rio de Janeiro
country: Brazil
facility: Brazilian National Cancer Institute
state: Other
city: Sao Paulo
country: Brazil
facility: Hospital Beneficencia Portuguesa
state: Other
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente (AC Camargo Cancer Center)
state: Other
city: Formosa
country: Brazil
facility: Instituto Brasileiro de Controle do Cancer
city: Edmonton
country: Canada
facility: University of Alberta / Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Other
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital
state: Other
city: Beijing
country: China
facility: Peking University People's Hospital
state: Other
city: Changchun
country: China
facility: Jilin University - First Affiliated Hospital - Cancer Center
state: Other
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Other
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Other
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Other
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Other
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Other
city: Guangzhou City
country: China
facility: Sun Yat-sen University Cancer Center
state: Other
city: Hangzhou City
country: China
facility: Zhejiang Cancer Hospital
state: Other
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Other
city: Shanghai
country: China
facility: Shanghai First People's Hospital
state: Other
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Other
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Other
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Other
city: Taiyuan
country: China
facility: Shanxi Province Cancer Hospital
state: Other
city: Urumqi
country: China
facility: The Affiliated Cancer Hospital of XinJiang Medical University
state: Other
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Other
city: Wuhan City
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Other
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Other
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Other
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Other
city: Yibin
country: China
facility: The Second People's Hospital of Yibin
state: Other
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
city: Brno-stred-Veveri
country: Czechia
facility: Fakultni nemocnice Brno
state: Other
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc (Fnol) - Onkologicka Klinika
state: Other
city: Praha 2
country: Czechia
facility: General University Hospital Prague
state: Other
city: Praha 8-Liben
country: Czechia
facility: Hospital Na Bulovce
state: Other
city: Kobenhavn
country: Denmark
facility: Rigshospitalet
state: Other
city: Turku
country: Finland
facility: University of Turku
state: Other
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Besancon Cedex
country: France
facility: Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz
state: Other
city: Bordeaux
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie
state: Other
city: Caen Cedex 5
country: France
facility: Centre de Lutte contre le Cancer - Francois Baclesse
state: Other
city: Cotes d'Armor
country: France
facility: CARIO - Centre Armoricain De Radiothérapie, D'imagerie Médicale Et D'oncologie
state: Other
city: Moselle
country: France
facility: Institute Cancer De Lorraine (ICL) - Alexis Vautrin
state: Other
city: Nantes Cedex 2
country: France
facility: Hopital Prive du Confluent
state: Other
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Avron (Hopital de la Croix Saint-Simon)
state: Other
city: Strasbourg
country: France
facility: Institut de cancerologie Strasbourg Europe
state: Other
city: Toulouse Cedex 9
country: France
facility: Institut Claudius Regaud IUCT-O
state: Other
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Other
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
state: Other
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Other
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE)
state: Other
city: Munchen
country: Germany
facility: University Hospital LMU Munich
state: Other
city: Budapest, Pest
country: Hungary
facility: National Institute of Oncology Hungary
state: Other
city: Debrecen, Hajdú-Bihar
country: Hungary
facility: Medical and Health Science Centre Debrecen Institution of Internal Medicine
state: Other
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Varmegyei Oktatokorhaz
state: Other
city: Waterford
country: Ireland
facility: University Hospital Waterford
state: Other
city: Catania
country: Italy
facility: Azienda Ospedaliera per l'Emergenza
state: Other
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Other
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino
state: Other
city: Vicenza
country: Italy
facility: Hospital San Bortolo
state: Other
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Other
city: Fukuoka
country: Japan
facility: Kurume University Hospital
state: Other
city: Gunma
country: Japan
facility: Gunma University Hospital
state: Other
city: Hidaka-City
country: Japan
facility: Saitama Cancer Center
state: Other
city: Hiroshima
country: Japan
facility: National Hospital Organization Kure Medical Center and Chugoku Cancer Center
state: Other
city: Kagoshima City
country: Japan
facility: Kagoshima University Hospital
state: Other
city: Kagoshima-City
country: Japan
facility: Kagoshima City Hospital
state: Other
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Other
city: Kashiwashi
country: Japan
facility: The Jikei University Kashiwa Hospital
state: Other
city: Kawasaki
country: Japan
facility: Nippon Medical School Musashi Kosugi Hospital
state: Other
city: Matsuyama
country: Japan
facility: NHO Shikoku Cancer Center
state: Other
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Other
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital
state: Other
city: Okayama
country: Japan
facility: Okayama University Hospital
state: Other
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Other
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
state: Other
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Other
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Other
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
state: Other
city: Sunto-Gun
country: Japan
facility: Shizuoka Cancer Center
state: Other
city: Tokyo
country: Japan
facility: Jikei University Hospital
state: Other
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Other
city: Tokyo
country: Japan
facility: Keio University Hospital
state: Other
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
state: Other
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Other
city: Akashi
country: Japan
facility: Hyogo Cancer Center
city: Ehime
country: Japan
facility: Ehime University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
state: Other
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Other
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Other
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
state: Other
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Other
city: Busan
country: Korea, Republic of
facility: Inje University Busan-Paik Hospital
city: Changwon, Kyungsangnam-do
country: Korea, Republic of
facility: Sungkyunkwan University of Medicine - Samsung Changwon Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: San Luis Potosi
country: Mexico
facility: Oncologico Potosino
state: Other
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
state: Other
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Other
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Other
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum Daniel Den Hoed
state: Other
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
state: Other
city: Olso
country: Norway
facility: Oslo University Hospital, Radiumhospitalet
state: Other
city: Trondheim
country: Norway
facility: Trondheim University Hospital, Trondheim
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: Białystok
country: Poland
facility: Białostockie Centrum Onkologii
state: Other
city: Singapore
country: Singapore
facility: National University Cancer Institute, Singapore
state: Other
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
state: Other
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Other
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
state: Other
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Other
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Other
city: Linköping
country: Sweden
facility: Linkoping University Hospital
state: Other
city: Lund
country: Sweden
facility: Skanes University Hospital - Universitetssjukhus
state: Other
city: Uppsala
country: Sweden
facility: Uppsala University Hospital (Akademiska Sjukhuset)
state: Other
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hospital
state: Other
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
state: Other
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
state: Other
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Other
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
state: Other
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Other
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Other
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: