Recurrent Platinum-Resistant Ovarian Cancer 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: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Vascular Biogenics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet ALL of the following criteria will be considered for enrollment into this study: 1. Signed informed consent must be obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements. 2. Female patients =18 years of age. 3. Histologically confirmed epithelial ovarian cancer (including primary peritoneal and fallopian tube) and documented disease. 4. Patients must have platinum-resistant disease, defined as a CT confirmed progressive disease within 90 to 180 days from completion of a minimum of 4 platinum therapy cycles (the time should be calculated from the last administered dose of platinum therapy to the day of CT confirming progression), or a platinum-refractory disease defined as CT confirmed progression during platinum therapy or up to 90 days from the last administered dose of platinum therapy. 5. Patients must have disease that is measurable according to RECIST 1.1 and require chemotherapy treatment. 6. ECOG PS 0–1. 7. Adequate hematological functions: a. ANC = 1500/mm3 b. PLT = 100,000/mm3 c. PT and PTT (seconds) 12 months duration and age > 45 years, or has undergone hysterectomy and/or bilateral oophorectomy. 11. Patients who are known to carry a BRCA mutation may be enrolled only after failing a PARP inhibitor treatment, or being intolerant of, or ineligible for PARP inhibitor treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Patients who meet ANY of the following criteria will be excluded from participation in this study: 1. Non-epithelial tumors (for example carcino-sarcomas). 2. Ovarian tumors with low malignant potential (i.e. borderline tumors), clear cell carcinomas, grade 1 serous tumors or mucinous adenocarcinomas. 3. History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled skin basal-cell carcinoma, adequately controlled, nonmetastatic squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. 4. Previous ovarian cancer treatment with >5 anticancer regimens. 5. Patients who had evidence of disease progression during or up to 90 days from the first line of platinum based therapy. 6. Treatment with another anti-cancer therapy within 14 days of randomization; or current or recent treatment with another investigational drug within 30 days of day of randomization; or previous randomization to this study. 7. Patients who received anti-angiogenic therapy (including anti-angiogenic Tyrosine Kinase Inhibitors) within the previous 4 weeks prior to day of randomization. 8. Any prior radiotherapy to the pelvis or whole abdomen (vaginal brachytherapy is allowed). 9. Surgery (including open biopsy) within 4 weeks prior to day of randomization, or anticipation of the need for major surgery during study treatment. 10. Minor surgical procedures, within 24 hours prior to day of randomization. 11. Patients with an ongoing requirement for significant immunosuppressive treatment, including the use of cyclosporine, or with a history of chronic use of any such medication within the last 4 weeks prior to day of randomization, excluding inhaled, topical and intra-articular steroids. A stable dose (e.g. started at least 2 weeks prior to randomization) of corticosteroids is allowed if the dose is ULN (Exception: documented Gilbert’s disease patients can be enrolled) b. alkaline phosphatase, AST/SGOT or ALT/SGPT =2.5 x ULN (or = 5 x ULN in the presence of liver metastases). 13. Inadequate renal function, defined as serum creatinine > ULN, unless calculated creatinine clearance > 50ml/min (by Cockroft & Gault formula). 14. Known history of testing positive for HIV, HBV or HCV. NOTE: patients with serology positive for HBV indicating past exposure but without evidence for active infection (e.g. negative PCR) are eligible. 15. CTCAE v5 Grade 2 or greater neuropathy (motor or sensory) from comorbidity, such as diabetes, or prior chemotherapy. 16. New York Heart Association (NYHA) Grade II or greater congestive heart failure. 17. History of myocardial infarction or unstable angina within 6 months prior to day of randomization. 18. History of stroke or transient ischemic attack within 6 months prior to day of randomization. 19. Patient with proliferative and/or vascular retinopathy. 20. Known brain metastasis. 21. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day of randomization. 22. History of hemoptysis (>1/2 teaspoon of bright red blood per episode) or active GI bleeding within 6 months prior to day of randomization. 23. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). 24.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of the combination of intravenous administration of VB-111 and paclitaxel compared to placebo and paclitaxel in patients with platinum resistant ovarian cancer as measured by overall survival (OS) and by progression free survival (PFS) by RECIST 1.1. - To examine the safety and tolerability of the combination of intravenous administration of VB-111 and paclitaxel compared to placebo and paclitaxel in patients with platinum resistant ovarian cancer;Secondary Objective: To evaluate: - Combined CA-125 (GCIG) and RECIST 1.1 objective response rate - Objective response rate (ORR) by RECIST 1.1 - CA-125 objective response rate (GCIG) - OS100 for a sensitivity analysis of OS;Primary end point(s): The primary efficacy endpoint are Overall Survival (OS) and Progression Free Survival (PFS). Demonstration of a treatment effect on at least one of the two endpoints is sufficient to support a conclusion of efficacy. ;Timepoint(s) of evaluation of this end point: Patients will be followed for survival until deceased for a maximum of 5 years after randomization. After study treatment discontinuation, follow-up will be performed every 2-3 months for the first 2 years, then every 5-6 months for the next 3 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Enpoints: - Combined CA-125 and RECIST responser rate according to GCIG definitions is the proportion of patients who have a response by CA-125 (GCIG) or RECIST 1.1 as specifiedin the SAP. - Objective response rate using RECIST 1.1 is the proportion of patients who have a partial or complete response according to RECIST 1.1 criteria. - CA-125 response rate(GCIG) is the proportion of patients who have a CA-125 response according to the criteria listed in section 8.2 of the protocol. - OS100, overall survival estimated from 100 days after randomization, as a sensitivity analysis of OS.;Timepoint(s) of evaluation of this end point: - Tumor assessment is performed every 12 weeks (±7 days) from randomization until discontinuation of study treatment or disease progression (whichever occurs later). For patients who discontinue study treatment prior to PD per RECIST, follow up scans should be performed every 12 weeks (± 7 days) until PD per RECIST for a maximum of 5 years after randomization - CA-125 response is assessed every 28 days (±3 days), starting from screening and until “treatment completion” visit - OS100 (overall survival estimated from 100 days after randomization) the interim analysis of OS should take place about 6 months after the end of the accrual. | — |
Countries
Bulgaria, Croatia, Israel, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactVBL Clinical Department
Vascular Biogenics Ltd. (VBL Therapeutics)
Outcome results
None listed