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

Recurrent Platinum Resistant Ovarian Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03398655
• Other study ID #: VB-111-701/GOG-3018
• Status: Completed
• Phase: Phase 3
• Start date: December 19, 2017
• Est. completion date: July 19, 2022

Study information

• Verified date: June 2021
• Source: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 408
• Est. completion date: July 19, 2022
• Est. primary completion date: July 19, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Recurrence
• 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
• Placebo + Paclitaxel
Placebo will be administered intravenously every 2 months Paclitaxel will be administered intravenously at a dose of 80mg/m2 every week

Locations

Country	Name	City	State
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Tzedek Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center, Department of Oncology	Rehovot
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Aichi Cancer Center	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Hokkaido University Hospital	Sapporo
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai	Myagi
Japan	Iwate Medical University Hospital	Shiwa-gun	Iwate
Japan	National Defense Medical College Hospital	Tokorozawa	Saitama
Japan	Ehime University Hospital	Toon	Ehime
Poland	Centrum Badan Klinicznych Jagiellonskiego Centrum Innowacji	Kraków
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	MedPolonia Sp. z o.o.	Poznan
Spain	Institut Català d'Oncologia - Hospital Duran i Reynals	Barcelona
Spain	Parc Taulí Hospital Universitari Edifici Santa Fe, Planta 0, Sala de recerca 3	Barcelona
Spain	Hospital Universitario de Donostia Edificio Onkologikoa- Planta baja, Sala de Ensayos Clinicos	Donostia
Spain	Hospital Gregorio Marañon Módulo prefabricado Oncología, Planta Baja	Madrid
Spain	Hospital Universitario Clínico San Carlos.	Madrid
Spain	MD Anderson Cancer Center Madrid Unidad de ensayos Clinicos	Madrid
Spain	Hospital Universitario Virgen del Rocío Servicio Oncología Médica. Ensayos Clínicos. Edificio CDCA	Sevilla
Spain	Consorcio Hospitalario General Universitario de Valencia Servicio de Oncología Médica - Unidad de Investigación	Valencia
Spain	Instituto Valenciano de Oncología Médica (IVO	Valencia
United States	Women's Cancer Care Associates, LLC	Albany	New York
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Texas Oncology, Austin Central - USO	Austin	Texas
United States	University of Maryland	Baltimore	Maryland
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	UAB Division of GYN Oncology	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Universtiy of Vermont	Burlington	Vermont
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Henry Ford Health Hospital	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University-Duke Cancer Institute	Durham	North Carolina
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Sanford Medical Center	Fargo	North Dakota
United States	Parkview Cancer Institute	Fort Wayne	Indiana
United States	UF Health	Gainesville	Florida
United States	Western Regional Medical Center	Goodyear	Arizona
United States	GHS Cancer Institute	Greenville	South Carolina
United States	Hartford Healthcare	Hartford	Connecticut
United States	Hartford HealthCare Cancer Institute at the Hospital of Central Ct	Hartford	Connecticut
United States	Westchester Medical Center	Hawthorne	New York
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Hermann	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	St. Vincent Gynecologic Oncology	Indianapolis	Indiana
United States	Womens Cancer Center/Kettering Cancer Care	Kettering	Ohio
United States	Northwell Health Cancer Institute	Lake Success	New York
United States	Dartmouth- Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	UCLA-JCCC-Women's Health Clinical Research Unit	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Marshfield Clinic Cancer Care & Research Center	Marshfield	Wisconsin
United States	University of Miami	Miami	Florida
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Atlantic Health System/Morristown Medical Center	Morristown	New Jersey
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	University of Oklahoma Health Sciences Center-Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange	Orange	California
United States	University of California, Irvine Medical Center/Chao Family Comprehensive Cancer Center	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates, PC - HAL - USO	Phoenix	Arizona
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Health Quest Medical Practice, Division of Gynecology/Oncology Gyno Dyson Cancer Center Vassar Brothers Medical Center	Poughkeepsie	New York
United States	UT Health	San Antonio	Texas
United States	University of California - San Francisco	San Francisco	California
United States	Sansum Clinic - USO	Santa Barbara	California
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Sanford Clinical Research	Sioux Falls	South Dakota
United States	Olive View UCLA Medical Center	Sylmar	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Arizona Oncology Associates, PC - HAL - USO	Tempe	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	Midwestern Regional Medical Center, Inc	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Vascular Biogenics Ltd. operating as VBL Therapeutics	GOG Foundation

Countries where clinical trial is conducted

United States,  Israel,  Japan,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From randomization until death from any cause (up to 5 years after last study treatment)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   VBL Therapeutics Company Website