Clinical Trials /

A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)

NCT03657043

Description:

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).

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)
  • Official Title: Open Label Phase 2 Study of Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With a Safety Run-in of a Dose-Dense Regimen

Clinical Trial IDs

  • ORG STUDY ID: SGNTV-002
  • NCT ID: NCT03657043

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer

Interventions

DrugSynonymsArms
tisotumab vedotinPart A: Tisotumab Vedotin

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).

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 (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.
    

Trial Arms

NameTypeDescriptionInterventions
Safety Run-In (3Q4W Schedule)Experimental28-day, 3 dose cycle
  • tisotumab vedotin
Part A: Tisotumab VedotinExperimental21-day, single dose cycle
  • tisotumab vedotin
Part A: Tisotumab Vedotin (3Q4W Schedule)Experimental28-day, 3 dose cycle
  • tisotumab vedotin
Part B: Tisotumab Vedotin (3Q4W Schedule)Experimental28-day, 3 dose cycle
  • tisotumab vedotin

Eligibility Criteria

        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 1 to 3 anticancer lines
             of therapy overall, including at least 1 line of therapy containing bevacizumab or
             biosimilar.

               -  Adjuvant ± neoadjuvant are considered 1 line of therapy.

               -  Patients may have received a PARP inhibitor or an immuno-oncology (IO) agent; any
                  of these regimens are to be considered a line of therapy for the purposes of this
                  study if not used as maintenance therapy.

               -  Maintenance therapy (including bevacizumab, PARP inhibitors and IOs) will be
                  considered part of the preceding line of therapy and not to be counted as a new
                  line of therapy.

               -  Any chemotherapy regimen change due to toxicity in the absence of disease
                  progression is considered as part of the same line of therapy.

               -  Hormonal therapy will be not be counted towards the lines of therapy.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs) (Safety Run-in only)
Time Frame:Up to 28 days
Safety Issue:
Description:Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

Secondary Outcome Measures

Measure:Incidence of adverse events that are Grade 3+, treatment-related, or serious (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Confirmed and unconfirmed ORR (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
Measure:Cancer Antigen 125 (CA-125) response rate according to Gynecologic Cancer Intergroup (GCIG) criteria (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Proportion of patients who have at least a 50% reduction in CA-125 value from baseline
Measure:Overall response according to the Gynecological Cancer Intergroup (GCIG) combined RECIST and CA-125 criteria (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Proportion of patients whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria
Measure:Duration of response (DOR) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or death due to any cause, whichever comes first
Measure:Disease control rate (DCR) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD)
Measure:Time to response (TTR) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)
Measure:Progression-free survival (PFS) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first
Measure:Overall survival (OS) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Time from the start of study treatment to date of death due to any cause
Measure:Pharmacokinetic (PK) parameter: Cmax (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Maximum observed concentration
Measure:PK parameter: AUClast (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
Measure:Incidence of antitherapeutic antibodies (ATA) (Parts A and B)
Time Frame:Up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Seagen Inc.

Trial Keywords

  • Platinum-resistant
  • Antibody drug conjugate
  • Tisotumab vedotin
  • PROC
  • Seattle Genetics

Last Updated

May 18, 2021