Patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (hereafter collectively referred to as platinum-resistant ovarian cancer and abbreviated as PROC) MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasm
Conditions
Interventions
Product Name: Tisotumab vedotin
Product Code: HuMax-TF-ADC
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TISOTUMAB VEDOTIN
CAS Number: 1418731-10-8
Other d
Sponsors
Seagen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding carcinosarcoma, mucinous, and low grade serous histologies), hereafter referred to as “ovarian cancer”. 2. Safety run-in patients only: Platinum-resistant ovarian cancer (PROC), which is defined as having progressed or relapsed within 6 months after previous platinum-containing chemotherapy and for which single agent chemotherapy is appropriate. Progression or relapse must be documented radiographically using RECIST v1.1 criteria. The patient may have received more than 1 prior systemic treatment regimen in the PROC setting. 3. Part A and Part B patients only: PROC; with the following prior treatment requirements: - The patient must have received 1 to 3 prior anticancer lines of therapy overall, including at least 1 line of therapy containing bevacizumab or a biosimilar to bevacizumab. - 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. 4. Measurable disease according to RECIST v1.1 as assessed by the investigator, defined as: a. A minimum of one non-nodal lesion =10 mm in the longest diameter from a non-irradiated area. If target lesion(s) are located within previously irradiated area only, the patient can be enrolled only if there has been demonstrated progression in the “in field” lesion and upon approval of the sponsor’s medical monitor. OR b. Lymph node lesion =15 mm in the shortest diameter from a non-irradiated area. 5. Age 18 years or older. 6. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 (see Appendix E for conversion of performance status using Karnofsky and Lansky scales, if applicable). 7. The following baseline laboratory data: ? Absolute neutrophil count (ANC) =1500/µL assessed at least 2 weeks after growth factor support, if applicable. ? Platelet count =100 x 109/L assessed at least 2 weeks after transfusion with blood products. ? Hemoglobin =5.6 mmol/L (9.0 g/dL) assessed at least 2 weeks after transfusion with blood products. ? Serum bilirubin =1.5 x upper limit of normal (ULN) or direct bilirubin =2 x ULN in patients diagnosed with Gilbert’s syndrome. ? Estimated glomerular filtration rate (eGFR) =50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable ? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 x ULN. (If liver tumor/metastases are present, then <5 x ULN is allowed). 8. Acceptable coagulation status: ? INR =1.2 without anticoagulation therapy. ? aPTT =1.25 ULN. 9. Life expectancy of at least 3 months. 10. Patients of childbearing potential as defined in Section 4.3, under the following conditions: ? Must have a negative serum or urine pregnancy test (minimum sensitivity 25 mIU/mL or equivalent units of beta human chorionic gonadotropin [ß-hcg]) result within 7 da
Exclusion criteria
Exclusion criteria: 1.Primary platinum-refractory disease, defined as disease progression within 3 months of completion of first line platinum-based therapy. 2. Patients with clinical symptoms or signs of gastrointestinal obstruction within the past 6 months or who currently require parenteral nutrition. 3.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; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry. 4. Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension (systolic BP >150 mmHg or diastolic BP >90 mmHg), unstable angina, acute myocardial infarction within 6 months prior to screening, serious cardiac arrhythmia requiring medication (not including asymptomatic atrial fibrillation with controlled ventricular rate); any medical history of congestive heart failure (Class II or higher as classified by the New York Heart Association, see Appendix H), or any medical history of decreased cardiac ejection fraction of <45%. 5. Ophthalmological: Active ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Patients with any prior episode of cicatricial conjunctivitis or Stevens Johnson syndrome (as evaluated by the investigator) are ineligible. Cataract is not considered active ocular surface disease for this study. 6.History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival =90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ, or stage I uterine cancer. 7.Inflammatory bowel disease including Crohn’s disease and ulcerative colitis 8.Ongoing, acute, or chronic inflammatory skin disease. 9.Uncontrolled tumor-related pain 10.Inflammatory lung disease, including moderate and severe asthma and chronic obstructive pulmonary disease, requiring chronic medical therapy 11.Grade 3 or higher pulmonary disease unrelated to underlying malignancy 12.Patients with significant peripheral vascular disease 13.Uncontrolled pleural or pericardial effusions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (Safety run-in) Evaluate safety and tolerability of a dose-dense regimen of tisotumab vedotin (Parts A and B) Evaluate antitumor activity of tisotumab vedotin;Secondary Objective: Evaluate the safety and tolerability of tisotumab vedotin Evaluate preliminary antitumor activity of tisotumab vedotin Evaluate antitumor activity of tisotumab vedotin Evaluate durability of response in patients who respond to tisotumab vedotin Evaluate stability and control of disease Evaluate the timing of responses Evaluate PFS of patients treated with tisotumab vedotin Evaluate survival of patients treated with tisotumab vedotin Assess pharmacokinetics of tisotumab vedotin Assess immunogenicity of tisotumab vedotin ;Primary end point(s): Incidence of DLTs or other unacceptable toxicities Investigator-determined confirmed ORR as measured by RECIST v1.1;Timepoint(s) of evaluation of this end point: Safety and tolerability will be assessed at every visit and via phone calls as needed between visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The confirmed and unconfirmed ORR according to RECIST v1.1, CA-125 response rate, combined RECIST/CA-125 overall response rate, and the DCR will be estimated and the 95% CIs will be calculated.;Timepoint(s) of evaluation of this end point: Radiographic tumor assessments | — |
Countries
Belgium, Denmark, Ireland, Italy, Spain, United States
Contacts
Public ContactSeagen Clinical Trial Information
Seagen Inc.
Outcome results
None listed