A Trial of Tisotumab Vedotin in Cervical Cancer
- Registration Number
- NCT03438396
- Lead Sponsor
- Seagen Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 102
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single arm tisotumab vedotin tisotumab vedotin (IV), 2.0 mg/kg, every 3 weeks (1Q3W)
- Primary Outcome Measures
Name Time Method Percentage of Participants With Confirmed Objective Response (OR) as Assessed by the Independent Review Committee (IRC) From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 20 months) The confirmed OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based upon RECIST v1.1, assessed by the IRC. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (Not Evaluable \[NE\]) scan evaluations between response scan and confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
- Secondary Outcome Measures
Name Time Method DOR as Assessed by the Investigator From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented PD verified by investigator or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Time to Response (TTR) as Assessed by the IRC From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the IRC. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Duration of Response (DOR) as Assessed by the IRC From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The DOR is defined as the duration from the first documented response of CR or PR (the start date of response, not the date when response was confirmed) to the date of the first documented progression disease (PD) verified by IRC or death. Based upon RECIST v1.1, the CR is defined as disappearance of all target and non-target lesions and no new lesions; the PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion; and the PD is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The DOR was estimated using Kaplan-Meier method.
Progression Free Survival (PFS) as Assessed by the IRC From Day 1 through IRC verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the IRC or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
Plasma Concentrations of Tisotumab Vedotin (HuMax-TF), Tisotumab Vedotin Antibody-drug Conjugate (HuMax-TF-ADC), and Free Monomethyl Auristatin E (MMAE) Predose and end of infusion of Cycle 1 Day 1 (C1D1) and Cycle 6 Day 1 (C6D1) Plasma concentrations of HuMax-TF, HuMax-TF-ADC, and Free MMAE measures on Cycle 1 Day 1 (predose and end of infusion) and Cycle 6 Day 1 (predose and end of infusion) are reported.
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tisotumab Vedotin Predose of each treatment cycle (Cycle 1 to 21) and end of treatment visit (approximately 49 months) Number of participants with positive ADA titer to tisotumab vedotin at baseline and post-baseline are reported. Baseline is defined as the latest available measurement made before the first dose of tisotumab vedotin. For post-baseline results, a participant was considered ADA positive if either ADA is negative at baseline and at least one post-baseline result is positive or positive at baseline and at least one positive post-baseline result with a titer higher than baseline.
Percentage of Participants With Confirmed OR as Assessed by the Investigator From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The confirmed OR is defined as best overall response of confirmed CR or confirmed PR based upon RECIST v1.1, assessed by the investigator. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as 2 CRs (CR-CR sequence) that were separated by at least 4 weeks with no evidence of progression in-between. The PR is defined as ≥ 30% decrease in the sum of diameters of target lesions (compared to baseline) and no unequivocal progression of existing non-target lesions and no new lesion. A confirmed PR is defined as PR-PR sequence or PR-CR sequence that were separated by at least 4 weeks. The intermediate missing (NE) scan evaluations between the response scan and the confirmation scan were allowed, eg, PR-NE-PR and PR-NE-NE-PR was considered PR confirmed (a repeat scan not earlier than 4 weeks after initial scan documenting response). 95% CI was calculated using the Clopper-Pearson method.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs From Day 1 through 30 days after the last dose of study drug (approximately 49 months) Laboratory abnormalities that induced clinical signs or symptoms, required concomitant therapy or required changes during treatment emergent period were reported as TEAEs. Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
PFS as Assessed by the Investigator From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The PFS is defined as the time from the start of study drug until the first documentation of PD based on RECIST v1.1, as assessed by the investigator or death due to any cause, whichever occurred first. The PD based upon RECIST v1.1 is defined as at least 20% increase in the sum of diameters of target lesions (compared to baseline), unequivocal progression of existing non-target lesions, and/or new lesion. The PFS was estimated using Kaplan-Meier method.
TTR as Assessed by the Investigator From Day 1 through investigator verified disease progression, initiation of new anticancer therapy, study withdrawal, or death, whichever occurred first (approximately 49 months) The TTR is defined as the duration from the start of study drug to the first documented response of either CR or PR based on RECIST v1.1, assessed by the investigator. A confirmed CR is defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as 2 PRs (≥ 30% decrease in the sum of diameters of target lesions compared to baseline and no unequivocal progression of existing non-target lesions and no new lesion) or an un-confirmed PR and an un-confirmed CR or achieved PR-NE-PR or PR-NE-NE-PR that were separated by at least 4 weeks with no evidence of progression in-between.
Overall Survival (OS) From Day 1 until death or withdrawal from the study, whichever occurred first (approximately 49 months) The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) From Day 1 through 30 days after the last dose of study drug (approximately 49 months) An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is "medically important"\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of tisotumab vedotin and 30 days after the last dose received.
Trial Locations
- Locations (53)
UZLeuvenGynaecologische oncologie
🇧🇪Leuven, Belgium
UCLA Dept. of OBGYN
🇺🇸Los Angeles, California, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
University of Gynecologic Oncology
🇺🇸Atlanta, Georgia, United States
Women's Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium
Southern Baptist Hospital of Florida, Inc
🇺🇸Jacksonville, Florida, United States
Community Hospital East
🇺🇸Indianapolis, Indiana, United States
Louisville Oncology
🇺🇸Louisville, Kentucky, United States
University of New Mexico Comprehensive Cancer Center (UNMCCC)
🇺🇸Albuquerque, New Mexico, United States
MD Anderson Cancer Center at Cooper University Hospital
🇺🇸Camden, New Jersey, United States
Oklahoma Cancer Specialists and Research Institute, LLC
🇺🇸Tulsa, Oklahoma, United States
Abington Memorial Hospital
🇺🇸Willow Grove, Pennsylvania, United States
Bon Secours Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
AZ Sint-Jan Brugge-Oostende av
🇧🇪Brugge, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Algemeen Ziekenhuis Maria MiddelaresMedical Oncology - IKG
🇧🇪Gent, Belgium
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Belgium
CHC SAINT Montlegia
🇧🇪Liège, Belgium
Centre Hospitalier de l'Ardenne
🇧🇪Libramont, Belgium
CHU de LIEGE/ Oncologie Médicale, domaine universitaire du Sart Tilman
🇧🇪Liege, Belgium
Nemocnice Na Bulovce, Gynekologicko-porodnicka kl
🇨🇿Prague, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Prague, Czechia
CHU UCL Namur site de Sainte Elisabeth
🇧🇪Namur, Belgium
Fakultni Nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Olomouc Onkologic
🇨🇿Olomouc, Czechia
Kliniken Essen-Mitte
🇩🇪Duesseldorf, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Klinikum der Universität München
🇩🇪Münich, Germany
Hospital Teresa Herrera-CHUAC
🇪🇸A Coruna, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Duran I Reynals ICO Hospitalet
🇪🇸Hospitalet de Llobregat, Spain
Hospital Universitario La Paz, Edificio dotacional de Oncología
🇪🇸Madrid, Spain
Fundacion Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain
Skåne University Hospital
🇸🇪Lund, Sweden
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Policlinico S.Orsola-Malpighi, SSD Oncologia Medica Addarii
🇮🇹Bologna, Italy
Irst Irccs
🇮🇹Meldola, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Naples, Italy
Policlinico Universitario Agostino Gemelli, UOC Patologia Ostetrica e Ginecologica
🇮🇹Rome, Italy
University of Alabama
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associate - Biltmore Cancer Center
🇺🇸Phoenix, Arizona, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Clínica Universidad de Navarra (Sede Madrid)
🇪🇸Madrid, Spain
The Ohio State University Wexner Medical Center
🇺🇸Hilliard, Ohio, United States
UT Health McGovern Medical School
🇺🇸Houston, Texas, United States
Froedtert & Medical College Clinics
🇺🇸Milwaukee, Wisconsin, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
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