Clinical trial NCT03786081: Safety and Efficacy of Tisotumab Vedotin Monotherapy & in Combination With Other Cancer Agents in Subjects With Cervical Cancer
Official title: A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) Monotherapy and in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: cervical carcinoma
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: GOG Foundation
name: Merck Sharp & Dohme LLC
First posted: 2018-12-24
Enrollment: 214
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, multi-center trial of tisotumab vedotin monotherapy and in combination with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB cervical cancer.

The trial consists of two-parts a dose escalation part and an expansion part. The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the combinations have been determined in the dose escalation part.

Detailed description: The dose escalation part will occur in participants with cervical cancer who have progressed during or after standard of care therapy and who are intolerant or ineligible to receive standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of tisotumab vedotin.

The dose expansion part of this study (Arms D through H) will be conducted in 2 populations: participants with cervical cancer who have not received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E, and H) and participants with cervical cancer who have progressed on or after at least 1 but no more than 2 prior systemic therapies (Arms F and G).

Participants enrolled to Arms D, E, F and H will receive the RP2D of tisotumab vedotin established in the dose escalation part. Participants enrolled to Arm G will receive tisotumab vedotin weekly (at a dose lower than subjects in all other Arms) for three weeks and 1 week off (28-day treatment cycle).

Eligibility criteria: Inclusion Criteria:

* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after standard of care treatments or are ineligible or intolerant to standard of care for recurrent or stage IVB cervical cancer (Arms A, B and C only).
* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E, and H only).
* Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than two prior systemic therapies for recurrent or stage IVB cervical cancer (Arms F and G only).
* Must have baseline measurable disease per RECIST v1.1.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All Arms).
* Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration
* Participants of childbearing potential must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration.
* Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial (All Arms).

Exclusion Criteria:

* Has clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. (All Arms)
* Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral hydration and/or nutrition. Post-operative obstructions within 4 weeks of abdominal surgery are permitted. (All Arms)
* Has clinically significant bleeding issues or risks

  * Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon or more) (Arm A and bevacizumab-eligible participants in Arm H)
  * Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arms A and H only)
  * Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arms A and H only)
* Has active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible (All Arms).
* Clinically significant cardiac disease
* Requires anti-coagulation therapy (Arms A and H only)

Primary outcomes:
measure: Dose escalation: Dose Limiting Toxicities (DLTs)
timeFrame: DLTs will be identified during the first treatment cycle (21 day cycles)
measure: Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
timeFrame: approximately 2 years
Secondary outcomes:
measure: Number of adverse events (AEs)
timeFrame: up to 2 years
measure: Dose escalation: ORR per RECIST v1.1
timeFrame: approximately 2 years
measure: Duration of Response (DOR) per RECIST v1.1 by investigator assessment
timeFrame: approximately 2 years
measure: Time to Response (TTR) per RECIST v1.1 by investigator assessment
timeFrame: approximately 2 years
measure: Progression free survival (PFS) per RECIST v1.1 by investigator assessment
timeFrame: approximately 2 years
measure: Overall Survival (OS)
timeFrame: approximately 2 years
measure: Maximum concentration (Cmax) (All Arms except G)
timeFrame: Up to 42 days
measure: Cmax (Arm G only)
timeFrame: Up to 2 years
measure: Trough Concentration (Ctrough) (All Arms)
timeFrame: Up to 2 years
measure: Area under the concentration-time curve (AUC) (All Arms except G)
timeFrame: Through 21 days after first dose
measure: AUC (Arm G only)
timeFrame: Through 8 days after first dose
measure: Anti-drug antibodies (ADAs)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Orange
country: United States
facility: Univ California, Irvine Medical Center
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Research and Education Institute
state: California
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Oschner Clinic
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Montana Cancer Consortium
state: Montana
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Group
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hilliard
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Brown University - Women's and Infant Hospital
state: Rhode Island
city: Greenville
country: United States
facility: St Francis Hospital Cancer Center
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Center
state: Utah
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA)
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven,
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) de Liège
city: Loverval
country: Belgium
facility: Grand Hôpital de Charleroi
city: Namur
country: Belgium
facility: CHU UCL Namur
city: Namur
country: Belgium
facility: Sainte-Elisabeth
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha
country: Czechia
facility: Fakultni nemocnice Bulovka
city: Praha
country: Czechia
facility: Nemocnice Na Bulovce
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Catania
country: Italy
facility: Azienda Ospedaliera Cannizzaro
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie AMC
city: Amsterdam
country: Netherlands
facility: AMC Medical Research
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen (UMCG)
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht (UMC Utrecht)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Hospital 12 De Octubre
city: Adana
country: Turkey
facility: Baskent University Adana Application and Research Center
city: Ankara
country: Turkey
facility: Baskent University Ankara Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
state: South Glamorgan
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Strathclyde
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital- Sutton
state: Surrey
Study officials:
References: