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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03657043
Recruitment Status : Recruiting
First Posted : September 4, 2018
Last Update Posted : May 29, 2020
Sponsor:
Collaborator:
Genmab
Information provided by (Responsible Party):
Seattle Genetics, Inc.

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).

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Drug: tisotumab vedotin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2022


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) (Safety Run-in only) [ Time Frame: Up to 28 days ]
  2. 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


Secondary Outcome Measures :
  1. Incidence of adverse events that are Grade 3+, treatment-related, or serious (Parts A and B) [ Time Frame: Up to 3 years ]
  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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)

  8. 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

  9. 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

  10. Pharmacokinetic (PK) parameter: Cmax (Parts A and B) [ Time Frame: Up to 3 years ]
    Maximum observed concentration

  11. 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

  12. Incidence of antitherapeutic antibodies (ATA) (Parts A and B) [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03657043


Contacts
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Contact: Seattle Genetics Trial Information Support 8663337436 clinicaltrials@seagen.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
Seattle Genetics, Inc.
Genmab
Investigators
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Study Director: Leonardo Nicacio, MD Seattle Genetics, Inc.
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Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT03657043    
Other Study ID Numbers: SGNTV-002
First Posted: September 4, 2018    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 27, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seattle Genetics, Inc.:
Platinum-resistant
Antibody drug conjugate
Tisotumab vedotin
PROC
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases