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

• ClinicalTrials.gov Identifier: NCT03398655
• Recruitment Status: Completed
• First Posted: January 12, 2018
• Last Update Posted: January 10, 2023
• Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Collaborator: GOG Foundation
• Information provided by (Responsible Party): Vascular Biogenics Ltd. operating as VBL Therapeutics

Tracking Information

• First Submitted Date: January 7, 2018
• First Posted Date: January 12, 2018
• Last Update Posted Date: January 10, 2023
• Actual Study Start Date: December 19, 2017
• Actual Primary Completion Date: July 19, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2021)

• Overall Survival [ Time Frame: From randomization until death from any cause (up to 5 years after last study treatment) ]
• Progression Free Survival (PFS) by RECIST 1.1 [ Time Frame: From randomization until progression defined according to RECIST 1.1 or death, whichever occurs first (up to 5 years after last study treatment) ]

• Original Primary Outcome Measures (submitted: January 7, 2018): Overall Survival [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]

Current Secondary Outcome Measures (submitted: September 30, 2021)

• Combined CA-125 and RECIST 1.1 response (GCIG) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ]

Original Secondary Outcome Measures (submitted: January 7, 2018)

• Combined CA-125 and RECIST 1.1 response (GCIG) [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]
• CA-125 Response (GCIG) [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]
• Objective response rate (ORR) by RECIST 1.1 [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]
• Progression Free Survival (PFS) by RECIST 1.1 [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]
• Progression Free Survival (PFS) by irRECIST [ Time Frame: From date of study entry until the date of death from any cause (up to 5 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of VB-111 With Paclitaxel vs Paclitaxel for Treatment of Recurrent Platinum-Resistant Ovarian Cancer (OVAL)
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Recurrent Platinum Resistant Ovarian Cancer

Intervention

• Drug: VB-111 + Paclitaxel
  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
  Other Name: Ofranergene Obadenovec
• Drug: Placebo + Paclitaxel
  Placebo will be administered intravenously every 2 months Paclitaxel will be administered intravenously at a dose of 80mg/m2 every week

Study Arms

• Experimental: Arm 1
  VB-111 + Paclitaxel
  Intervention: Drug: VB-111 + Paclitaxel
• Active Comparator: Arm 2
  Placebo + Paclitaxel
  Intervention: Drug: Placebo + Paclitaxel

• Publications *: Arend RC, Monk BJ, Herzog TJ, Moore KN, Shapira-Frommer R, Ledermann JA, Tewari KS, Secord AA, Rachmilewitz Minei T, Freedman LS, Miller A, Shmueli SF, Lavi M, Penson RT. Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer. Gynecol Oncol. 2021 May;161(2):496-501. doi: 10.1016/j.ygyno.2021.02.014. Epub 2021 Feb 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 8, 2023): 408
• Original Estimated Enrollment (submitted: January 7, 2018): 350
• Actual Study Completion Date: July 19, 2022
• Actual Primary Completion Date: July 19, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Female patients ≥18 years of age
2. Histologically confirmed epithelial ovarian cancer and documented disease.
3. Patients must have platinum-resistant disease
4. Patients must have disease that is measurable according to RECIST 1.1 and require chemotherapy treatment.
5. ECOG PS 0-1.

6. 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.
7. 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:

1. Non-epithelial tumors (Carcino-sarcomas are excluded)
2. Ovarian tumors with low malignant potential (i.e. borderline tumors) clear cell carcinomas, grade 1 serous tumors or mucinous tumors.
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 basal-cell carcinoma, adequately controlled, non-metastatic 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. Any prior radiotherapy to the pelvis or whole abdomen.

6. 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).

7. Inadequate renal function, defined as:

   • Serum creatinine > ULN OR
   • Calculated creatinine clearance < 50ml/min (by Cockroft & Gault formula)
8. New York Heart Association (NYHA) Grade II or greater congestive heart failure
9. History of myocardial infarction or unstable angina within 6 months prior to day of randomization.
10. History of stroke or transient ischemic attack within 6 months prior to day of randomization.
11. Patient with proliferative and/or vascular retinopathy
12. Known brain metastases
13. History of hemoptysis or active GI bleeding within 6 month prior to day of randomization
14. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
15. History of abdominal fistula or gastrointestinal perforation.
16. Current signs and symptoms of bowel obstruction
17. Uncontrolled active infection
18. 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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, Japan, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03398655
• Other Study ID Numbers: VB-111-701/GOG-3018
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: GOG Foundation
• Investigators: Not Provided
• PRS Account: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Verification Date: June 2021