Clinical trial NCT03438396: A Trial of Tisotumab Vedotin in Cervical Cancer
Official title: A Single Arm, Multicenter, International Trial of Tisotumab Vedotin (HuMax®-TF-ADC) in Previously Treated, Recurrent or Metastatic Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genmab
name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Belgian Gynaecological Oncology Group
name: Gynecologic Oncology Group
First posted: 2018-02-19
Enrollment: 102
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Single arm, Multicenter, International Trial of Tisotumab Vedotin (HuMax®-TF-ADC) in Previously Treated, Recurrent or Metastatic Cervical Cancer.

Detailed description: The purpose of the trial is to evaluate the efficacy and safety/tolerability of tisotumab vedotin in patients with previously treated, recurrent or metastatic cervical cancer. Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue factor (TF), a protein aberrantly expressed in a wide number of tumors including cervical cancer. Preliminary safety and efficacy data observed in a cohort of previously treated cervical cancer patients suggest a positive benefit risk profile for this population of high unmet need.

Eligibility criteria: Inclusion Criteria

* Patients with extra-pelvic metastatic or recurrent cervical cancer including squamous cell, adenocarcinoma or adenosquamous histology who have experienced disease progressed on standard of care chemotherapy in combination with bevacizumab, if eligible.
* Measurable disease according to RECIST v1.1 as assessed by IRC.
* Age ≥ 18 years.
* Acceptable renal function
* Acceptable liver function
* Acceptable hematological status
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* A negative serum pregnancy test for patients of reproductive potential.
* All patients must provide a fresh or archival biopsy during screening.
* Following receipt of verbal and written information about the trial, patients must provide signed informed consent before any trial-related activity is carried out.

Exclusion Criteria

* Have received no more than 2 prior systemic treatment regimens for recurrent or metastatic cervical cancer.
* Known past or current coagulation defects leading to an increased risk of bleeding;
* Ongoing major bleeding
* Active ocular surface disease
* Known past or current malignancy other than the inclusion diagnosis.
* Peripheral neuropathy grade ≥ 2

Primary outcomes:
measure: Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC)
timeFrame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months)
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by the IRC
timeFrame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: Percentage of Participants With Confirmed OR as Assessed by the Investigator
timeFrame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: DOR as Assessed by the Investigator
timeFrame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: Time to Response (TTR) as Assessed by the IRC
timeFrame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: TTR as Assessed by the Investigator
timeFrame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: Progression Free Survival (PFS) as Assessed by the IRC
timeFrame: From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: PFS as Assessed by the Investigator
timeFrame: From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months)
measure: Overall Survival (OS)
timeFrame: From Day 1 until death or withdrawal from the study, whichever occurred first (approximately 49 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: From Day 1 through 30 days after the last dose of study drug (approximately 49 months)
measure: Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE)
timeFrame: Predose and end of infusion of Cycle 1 Day 1 (C1D1) and Cycle 6 Day 1 (C6D1)
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin
timeFrame: Predose of each treatment cycle (Cycle 1 to 21) and end of treatment visit (approximately 49 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Associate - Biltmore Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Dept. of OBGYN
state: California
city: Jacksonville
country: United States
facility: Southern Baptist Hospital of Florida, Inc
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: University of Gynecologic Oncology
state: Georgia
city: Indianapolis
country: United States
facility: Community Hospital East
state: Indiana
city: Louisville
country: United States
facility: Louisville Oncology
state: Kentucky
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center (UNMCCC)
state: New Mexico
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Hilliard
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC
state: Oklahoma
city: Willow Grove
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours Saint Francis Cancer Center
state: South Carolina
city: Houston
country: United States
facility: UT Health McGovern Medical School
state: Texas
city: Milwaukee
country: United States
facility: Froedtert & Medical College Clinics
state: Wisconsin
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende av
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Maria MiddelaresMedical Oncology - IKG
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZLeuvenGynaecologische oncologie
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Liege
country: Belgium
facility: CHU de LIEGE/ Oncologie Médicale, domaine universitaire du Sart Tilman
city: Liège
country: Belgium
facility: CHC SAINT Montlegia
city: Namur
country: Belgium
facility: CHU UCL Namur site de Sainte Elisabeth
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc Onkologic
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Prague
country: Czechia
facility: Nemocnice Na Bulovce, Gynekologicko-porodnicka kl
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Duesseldorf
country: Germany
facility: Kliniken Essen-Mitte
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Münich
country: Germany
facility: Klinikum der Universität München
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii
city: Meldola
country: Italy
facility: Irst Irccs
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli, UOC Patologia Ostetrica e Ginecologica
city: A Coruna
country: Spain
facility: Hospital Teresa Herrera-CHUAC
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Duran I Reynals ICO Hospitalet
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra (Sede Madrid)
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Edificio dotacional de Oncología
city: Palma de Mallorca
country: Spain
facility: Fundacion Hospital Son Llatzer
city: Lund
country: Sweden
facility: Skåne University Hospital
Study officials:
References:
citation: Coleman RL, Lorusso D, Gennigens C, Gonzalez-Martin A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindelov SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 May;22(5):609-619. doi: 10.1016/S1470-2045(21)00056-5. Epub 2021 Apr 9.