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

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ClinicalTrials.gov Identifier: NCT03398655
Recruitment Status : Recruiting
First Posted : January 12, 2018
Last Update Posted : October 12, 2021
Sponsor:
Collaborator:
GOG Foundation
Information provided by (Responsible Party):
Vascular Biogenics Ltd. operating as VBL Therapeutics

Tracking Information
First Submitted Date  ICMJE January 7, 2018
First Posted Date  ICMJE January 12, 2018
Last Update Posted Date October 12, 2021
Actual Study Start Date  ICMJE December 19, 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study of VB-111 With Paclitaxel vs Paclitaxel for Treatment of Recurrent Platinum-Resistant Ovarian Cancer (OVAL)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Platinum Resistant Ovarian Cancer
Intervention  ICMJE
  • 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  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2018)
400
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2018)
350
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shifra Fain-Shmueli 972-8-9935000 shifra@vblrx.com
Listed Location Countries  ICMJE Israel,   Japan,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03398655
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Vascular Biogenics Ltd. operating as VBL Therapeutics
Study Sponsor  ICMJE Vascular Biogenics Ltd. operating as VBL Therapeutics
Collaborators  ICMJE GOG Foundation
Investigators  ICMJE Not Provided
PRS Account Vascular Biogenics Ltd. operating as VBL Therapeutics
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP