Open Label Phase 2 Study of Tisotumab Vedotin for Patients with Platinum-Resistant Ovarian Cancer with a Safety Run-in of a Dose-Dense Regime
- Conditions
- 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: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001219-22-IT
- Lead Sponsor
- SEATTLE GENETICS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 182
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.
a. Subjects may or may not have received bevacizumab for treatment of ovarian cancer.
3. Part A and Part B patients only: PROC. The patient must have received at most 1 prior cytotoxic chemotherapy regimen in the PROC setting, and for whom single agent chemotherapy is appropriate as the next line of treatment. Patients eligible to receive a PARP inhibitor may have received such therapy; PARP inhibitors are not considered cytotoxic chemotherapy regimens for the purposes of this study.
4. Measurable disease according to RECIST v1.1 as assessed by the investigator, defined as:
a. A minimum of one non-nodal lesion = or >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 = or >15 mm in the shortest diameter from a nonirradiated 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) = or >1500/µL assessed at least 2 weeks after growth factor support, if applicable.
- Platelet count = or >100 x 109/L assessed at least 2 weeks after transfusion with blood products.
- Hemoglobin = or >5.6 mmol/L (9.0 g/dL) assessed at least 2 weeks after transfusion with blood products.
- Serum bilirubin = or <1.5 x upper limit of normal (ULN) or direct bilirubin = or <2 x ULN in patients diagnosed with Gilbert's syndrome.
- Estimated glomerular filtration rate (eGFR) = or >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) = or <2.5 x ULN. (If liver tumor/metastases are present, then <5 x ULN is allowed).
8. Acceptable coagulation status:
- INR = or <1.2 without anticoagulation therapy.
- aPTT = or <1.25 ULN.
9. Life expectancy of at least 3 months.
10. Patients of childbearing potential as in Section 4.3s:
- Negative serum or urine pregnancy test result within 7 days prior to the first dose of tisotumab vedotin.
- Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 6 months after the final dose of study drug administration.
- Must agree to complete abstinence or, if sexually active, must consistently use 2 highly effective methods of birth control starting at time of informed consent and continuing throughout the study and for at least 6 months after the final dose of study drug administration.
Are the trial subjects under 18? no
Number of subjects for this age r
1.Primary platinum-refractory disease, defined as disease progression within 2 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 = or >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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method