A Study of VB-111 With Paclitaxel vs Paclitaxel for Treatment of Recurrent Platinum-Resistant Ovarian Cancer (OVAL)

Study Overview
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Brief Summary
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The purpose of this phase 3, randomized, multicenter study is to compare VB-111 and paclitaxel to placebo and paclitaxel in adult patients with Recurrent Platinum-Resistant Ovarian Cancer.

Official Title
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A Randomized, Controlled, Double-Arm, Double-Blind, Multi-Center Study of Ofranergene Obadenovec (VB-111) Combined With Paclitaxel vs. Paclitaxel Combined With Placebo for the Treatment of Recurrent Platinum-Resistant Ovarian Cancer

Conditions
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Recurrent Platinum Resistant Ovarian Cancer

Intervention / Treatment
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* Drug: VB-111 + Paclitaxel
* Drug: Placebo + Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients ≥18 years of age Histologically confirmed epithelial ovarian cancer and documented disease. Patients must have platinum-resistant disease Patients must have disease that is measurable according to RECIST 1.1 and require chemotherapy treatment. ECOG PS 0-1. Adequate hematological functions: ANC ≥ 1000/mm3 PLT ≥ 100,000/mm3 PT and PTT (seconds) < 1.2 X ULN. Patients who are anticoagulated do not need to meet criteria for PT and PTT. Patients who are known to carry a BRCA mutation may be enrolled only after (following PARP inhibitor treatment failure, or being intolerant of, or ineligible for PARP inhibitor treatment). Exclusion Criteria: Non-epithelial tumors (Carcino-sarcomas are excluded) Ovarian tumors with low malignant potential (i.e. borderline tumors) clear cell carcinomas, grade 1 serous tumors or mucinous tumors. 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 basal-cell carcinoma, adequately controlled, non-metastatic squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Previous ovarian cancer treatment with >5 anticancer regimens. Any prior radiotherapy to the pelvis or whole abdomen. Inadequate liver function, defined as serum creatinine > ULN, unless calculated creatinine clearance > 50ml/min (by Cockroft & Gault formula): Serum (total) bilirubin > ULN (Exception: documented Gilbert's disease patients can be enrolled) Alkaline phosphatase, AST/SGOT or ALT/SGPT ≥2.5 x ULN (or ≥ 5 x ULN in the presence of liver metastases). Inadequate renal function, defined as: Serum creatinine > ULN OR Calculated creatinine clearance < 50ml/min (by Cockroft & Gault formula) New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months prior to day of randomization. History of stroke or transient ischemic attack within 6 months prior to day of randomization. Patient with proliferative and/or vascular retinopathy Known brain metastases History of hemoptysis or active GI bleeding within 6 month prior to day of randomization Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). History of abdominal fistula or gastrointestinal perforation. Current signs and symptoms of bowel obstruction Uncontrolled active infection Patients who had evidence of disease progression during or up to 90 days from the last dose of the first line of platinum based therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>VB-111 + Paclitaxel | Drug: VB-111 + Paclitaxel<br>* VB-111 will be administered intravenously at a dose of 1x10e13 VPs every 2 months Paclitaxel will be administered intravenously at a dose of 80mg/m2 every week<br>* Other names: Ofranergene Obadenovec;|
| Active Comparator: Arm 2<br>Placebo + Paclitaxel | Drug: Placebo + Paclitaxel<br>* Placebo will be administered intravenously every 2 months Paclitaxel will be administered intravenously at a dose of 80mg/m2 every week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From randomization until death from any cause (up to 5 years after last study treatment) | 
| Progression Free Survival (PFS) by RECIST 1.1 |  | From randomization until progression defined according to RECIST 1.1 or death, whichever occurs first (up to 5 years after last study treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined CA-125 and RECIST 1.1 response (GCIG) |  | From date of study entry until the date of death from any cause, or up to 5 years after last study treatment | 
| CA-125 Response (GCIG) |  | From date of study entry until the date of death from any cause, or up to 5 years after last study treatment | 
| Objective response rate (ORR) by RECIST 1.1 |  | From date of study entry until the date of death from any cause, or up to 5 years after last study treatment | 
| OS100 for a sensitivity analysis of OS |  | From 100 days after date of study entry until the date of death from any cause, or up to 5 years after last study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Ovarian cancer, Platinum resistant ovarian cancer, Ovarian cancer, Ovarian carcinoma, Epithelial ovarian cancer, paclitaxel