Purpose

This trial will study tisotumab vedotin to find out what its side effects are and to see if it works for platinum-resistant ovarian cancer (PROC). It will test different doses of tisotumab vedotin that are given at different times. It will also compare the side effects and ability to treat tumors of these different doses and schedules. In this study, there will be a safety run-in group of approximately 12 patients that will look at a dose-dense treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In addition to the safety run-in patients, there will be three groups in the study. One group will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
  • Safety run-in only: PROC. Patients may have received more than 1 prior systemic treatment regimen in the PROC setting.
  • Part A and Part B only: Patients with PROC who have received at most 1 prior cytotoxic chemotherapy regimen in the PROC setting
  • Measurable disease according to RECIST v1.1 as assessed by the investigator
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • Life expectancy of at least 3 months
  • Able to provide fresh or archival tissue for biomarker analysis

Exclusion Criteria

  • Primary platinum-refractory disease, defined as disease progression within 2 months of completion of first line platinum-based therapy
  • Patients with clinical symptoms or signs of gastrointestinal obstruction with the past 6 months or who currently require parenteral nutrition
  • Hematological: Known past or current coagulation defects leading to an increased risk of bleeding, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, or trauma with increased risk of life-threatening bleeding within 8 weeks of trial entry
  • Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension, unstable angina, acute myocardial infarction with 6 months of screening, serious cardiac arrhythmia requiring medication, medical history of congestive heart failure, or medical history of decreased cardiac ejection fraction of <45%
  • Ophthalmological: Active ocular surface disease at baseline or prior episode of cicatricial conjunctivitis or Stevens Johnson syndrome
  • Prior treatment with MMAE-derived drugs
  • Inflammatory bowel disease including Crohn's disease and ulcerative colitis
  • Ongoing, acute, or chronic inflammatory skin disease
  • Uncontrolled tumor-related pain
  • Inflammatory lung disease requiring chronic medical therapy
  • Grade 3 or higher pulmonary disease unrelated to underlying malignancy
  • Uncontrolled pleural or pericardial effusions
  • Grade >1 peripheral neuropathy
  • Patients who are pregnant or breastfeeding

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Safety Run-In (Dose-dense Schedule)
28-day, 3 dose cycle
  • Drug: tisotumab vedotin
    Intravenous (IV) infusion
Experimental
Part A: Tisotumab Vedotin
21-day, single dose cycle
  • Drug: tisotumab vedotin
    Intravenous (IV) infusion
Experimental
Part A: Tisotumab Vedotin (Dose-dense Schedule)
28-day, 3 dose cycle
  • Drug: tisotumab vedotin
    Intravenous (IV) infusion
Experimental
Part B: Tisotumab Vedotin (Dose-dense Schedule)
28-day, 3 dose cycle
  • Drug: tisotumab vedotin
    Intravenous (IV) infusion

Recruiting Locations

University of Kansas Cancer Center
Westwood, Kansas 66205
Contact:
Dewi Mouzoukos
913-588-6029
dmouzoukos@kumc.edu

More Details

Status
Recruiting
Sponsor
Seattle Genetics, Inc.

Study Contact

Seattle Genetics Trial Information Support
8663337436
clinicaltrials@seagen.com

Detailed Description

The study objectives are to evaluate the safety, antitumor activity, and pharmacokinetics of tisotumab vedotin (TV) administered every 3 weeks or on Days 1, 8, and 15 of every 4-week cycle (dose-dense regimen; 3Q4W) for patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has relapsed within 6 months of the completion of platinum-based treatment and determined to be platinum resistant. All patients must have PROC and be eligible for single agent chemotherapy.

The safety run-in period will evaluate the safety of a weekly schedule. The highest dose level that is considered safe will be the recommended phase 2 dose (RP2D) and will be used in Part A. In Part A, participants will be randomized in a 1:1 ratio to receive tisotumab vedotin intravenously (IV) every 3 weeks (Q3W regimen) or the safety run-in RP2D on Days 1, 8, and 15 of every 4-week cycle (weekly regimen; 3Q4W) if a RP2D has been identified. Participants who enroll in Part B will receive tisotumab vedotin on Days 1, 8, and 15 of every 4-week cycle (weekly regimen) at a pre-specified dose level, if the dose level is considered safe and tolerable in the safety run-in period.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.