Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer

Cervical Cancer Clinical Trial

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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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04697628
• Other study ID #: SGNTV-003
• Secondary ID: ENGOT cx-12GOG-3
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 22, 2021
• Est. completion date: August 5, 2025

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 568
• Est. completion date: August 5, 2025
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• tisotumab vedotin
2.0 mg/kg every 3 weeks (Q3W)
• topotecan
1 or 1.25 mg/m2 intravenous (IV) on Days 1 to 5, every 21 days
• vinorelbine
30 mg/m2 IV on Days 1 and 8, every 21 days
• gemcitabine
1000 mg/m2 IV on Days 1 and 8, every 21 days
• irinotecan
100 or 125 mg/m2 IV weekly for 28 days, every 42 days
• pemetrexed
500 mg/m2 IV on Day 1, every 21 days

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Genmab

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Poland,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to approximately 2 years
Secondary	Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator	PFS per investigator is defined as the time from the date of randomization to the first documentation of disease progression per RECIST v.1.1 by the investigator, or to date of death due to any cause, whichever occurs earlier.	Up to approximately 1 year
Secondary	Confirmed objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator	Confirmed objective response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1.	Up to approximately 6 months
Secondary	Time-to-response (TTR) as assessed by the investigator	TTR is defined as the time from the date of randomization to the date of first confirmed objective response (CR or PR that is subsequently confirmed). Only participants with confirmed CR or PR will be included in the analysis.	Up to approximately 6 months
Secondary	Duration of response (DOR) as assessed by the investigator	DOR is defined as the time from the date of first confirmed objective response (CR or PR that is subsequently confirmed) to the date of first documented PD per RECIST v1.1 or death from any cause, whichever occurs first. Only participants with confirmed CR or PR will be included in the analysis.	Up to approximately 1 year
Secondary	Incidence of adverse events (AEs)	Analyses of AEs will be summarized descriptively	Up to approximately 2 years
Secondary	Health-related quality of life as assessed by EQ-5D-5L index	EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	Up to approximately 2 years
Secondary	Health-related quality of life as assessed by EQ-5D visual analog scale (VAS)	EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of HRQOL that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system and the EQ VAS. The EQ VAS records the participant's self-rated health on a vertical VAS. This can be used as a quantitative measure of health outcome that reflects the participant's own judgment.	Up to approximately 2 years
Secondary	Health-related quality of life as assessed by EORTC-QLQ-C30	The QLQ-C30 is a validated questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess the quality of life of participants with cancer in multicultural clinical research settings.	Up to approximately 6 months
Secondary	Health-related quality of life as assessed by EORTC-QLQ-CX24	The EORTC-QLQ-CX24 is a validated questionnaire developed by the EORTC to assess the quality of life in patients who are treated for cervical cancer both in clinical studies and in clinical practice.	Up to approximately 6 months