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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03657043
Recruitment Status : Active, not recruiting
First Posted : September 4, 2018
Last Update Posted : May 18, 2021
Sponsor:
Collaborator:
Genmab
Information provided by (Responsible Party):
Seagen Inc.

Tracking Information
First Submitted Date  ICMJE August 22, 2018
First Posted Date  ICMJE September 4, 2018
Last Update Posted Date May 18, 2021
Actual Study Start Date  ICMJE March 20, 2019
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 19, 2019)
  • Incidence of dose limiting toxicities (DLTs) (Safety Run-in only) [ Time Frame: Up to 28 days ]
  • Confirmed objective response rate (ORR) (Parts A and B) [ Time Frame: Up to 3 years ]
    Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator
Original Primary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • Incidence of Dose Limiting Toxicities (DLTs) - Safety Run-In Phase [ Time Frame: Up to 60 days ]
  • Confirmed Objective Response Rate (ORR) - Phase 2 [ Time Frame: Up to 3 years ]
    Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2019)
  • Incidence of adverse events that are Grade 3+, treatment-related, or serious (Parts A and B) [ Time Frame: Up to 3 years ]
  • Confirmed and unconfirmed ORR (Parts A and B) [ Time Frame: Up to 3 years ]
    Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
  • Cancer Antigen 125 (CA-125) response rate according to Gynecologic Cancer Intergroup (GCIG) criteria (Parts A and B) [ Time Frame: Up to 3 years ]
    Proportion of patients who have at least a 50% reduction in CA-125 value from baseline
  • 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 ]
    Proportion of patients whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria
  • Duration of response (DOR) (Parts A and B) [ Time Frame: Up to 3 years ]
    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
  • Disease control rate (DCR) (Parts A and B) [ Time Frame: Up to 3 years ]
    Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD)
  • Time to response (TTR) (Parts A and B) [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)
  • Progression-free survival (PFS) (Parts A and B) [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first
  • Overall survival (OS) (Parts A and B) [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to date of death due to any cause
  • Pharmacokinetic (PK) parameter: Cmax (Parts A and B) [ Time Frame: Up to 3 years ]
    Maximum observed concentration
  • PK parameter: AUClast (Parts A and B) [ Time Frame: Up to 3 years ]
    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
  • Incidence of antitherapeutic antibodies (ATA) (Parts A and B) [ Time Frame: Up to 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • Incidence of adverse events that are Grade 3+, treatment-related, or serious - Phase 2 [ Time Frame: Up to 3 years ]
  • Confirmed and unconfirmed ORR - Phase 2 [ Time Frame: Up to 3 years ]
    Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
  • Cancer Antigen 125 (CA-125) response rate according to Gynecologic Cancer Intergroup (GCIG) criteria - Phase 2 [ Time Frame: Up to 3 years ]
    Proportion of patients who have at least a 50% reduction in CA-125 value from baseline
  • Overall response according to the Gynecological Cancer Intergroup (GCIG) combined RECIST and CA-125 criteria - Phase 2 [ Time Frame: Up to 3 years ]
    Proportion of patients whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria
  • Duration of response (DOR) - Phase 2 [ Time Frame: Up to 3 years ]
    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
  • Disease control rate (DCR) - Phase 2 [ Time Frame: Up to 3 years ]
    Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD)
  • Time to response (TTR) - Phase 2 [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)
  • Progression-free survival (PFS) - Phase 2 [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first
  • Overall survival (OS) - Phase 2 [ Time Frame: Up to 3 years ]
    Time from the start of study treatment to date of death due to any cause
  • Pharmacokinetic (PK) parameter: Cmax - Phase 2 [ Time Frame: Up to 3 years ]
    Maximum observed concentration
  • PK parameter: AUClast - Phase 2 [ Time Frame: Up to 3 years ]
    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
  • Incidence of antitherapeutic antibodies (ATA) - Phase 2 [ Time Frame: Up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
Intervention  ICMJE Drug: tisotumab vedotin
Intravenous (IV) infusion
Study Arms  ICMJE
  • Experimental: Safety Run-In (3Q4W Schedule)
    28-day, 3 dose cycle
    Intervention: Drug: tisotumab vedotin
  • Experimental: Part A: Tisotumab Vedotin
    21-day, single dose cycle
    Intervention: Drug: tisotumab vedotin
  • Experimental: Part A: Tisotumab Vedotin (3Q4W Schedule)
    28-day, 3 dose cycle
    Intervention: Drug: tisotumab vedotin
  • Experimental: Part B: Tisotumab Vedotin (3Q4W Schedule)
    28-day, 3 dose cycle
    Intervention: Drug: tisotumab vedotin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 17, 2021)
98
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2018)
142
Estimated Study Completion Date  ICMJE August 31, 2022
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Denmark,   Ireland,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03657043
Other Study ID Numbers  ICMJE SGNTV-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seagen Inc.
Study Sponsor  ICMJE Seagen Inc.
Collaborators  ICMJE Genmab
Investigators  ICMJE
Study Director: Francisco Beca, MD, PhD Seagen Inc.
PRS Account Seagen Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP