Clinical trial NCT03398655: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Platinum Resistant Ovarian Cancer
Keywords: Recurrent Ovarian cancer
Platinum resistant ovarian cancer
Ovarian cancer
Ovarian carcinoma
Epithelial ovarian cancer
paclitaxel
Lead sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: GOG Foundation
First posted: 2018-01-12
Enrollment: 408
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization until death from any cause (up to 5 years after last study treatment)
measure: Progression Free Survival (PFS) by RECIST 1.1
timeFrame: From randomization until progression defined according to RECIST 1.1 or death, whichever occurs first (up to 5 years after last study treatment)
Secondary outcomes:
measure: Combined CA-125 and RECIST 1.1 response (GCIG)
timeFrame: From date of study entry until the date of death from any cause, or up to 5 years after last study treatment
measure: CA-125 Response (GCIG)
timeFrame: From date of study entry until the date of death from any cause, or up to 5 years after last study treatment
measure: Objective response rate (ORR) by RECIST 1.1
timeFrame: From date of study entry until the date of death from any cause, or up to 5 years after last study treatment
measure: OS100 for a sensitivity analysis of OS
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Division of GYN Oncology
state: Alabama
city: Goodyear
country: United States
facility: Western Regional Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL - USO
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL - USO
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA-JCCC-Women's Health Clinical Research Unit
state: California
city: Orange
country: United States
facility: The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center/Chao Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic - USO
state: California
city: Sylmar
country: United States
facility: Olive View UCLA Medical Center
state: California
city: Hartford
country: United States
facility: Hartford HealthCare Cancer Institute at the Hospital of Central Ct
state: Connecticut
city: Hartford
country: United States
facility: Hartford Healthcare
state: Connecticut
city: Gainesville
country: United States
facility: UF Health
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center, Inc
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Gynecologic Oncology
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health Hospital
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth- Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Atlantic Health System/Morristown Medical Center
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Albany
country: United States
facility: Women's Cancer Care Associates, LLC
state: New York
city: Hawthorne
country: United States
facility: Westchester Medical Center
state: New York
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: Poughkeepsie
country: United States
facility: Health Quest Medical Practice, Division of Gynecology/Oncology Gyno Dyson Cancer Center Vassar Brothers Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University-Duke Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Kettering
country: United States
facility: Womens Cancer Center/Kettering Cancer Care
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center-Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: GHS Cancer Institute
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Clinical Research
state: South Dakota
city: Austin
country: United States
facility: Texas Oncology, Austin Central - USO
state: Texas
city: Houston
country: United States
facility: Memorial Hermann
state: Texas
city: San Antonio
country: United States
facility: UT Health
state: Texas
city: Burlington
country: United States
facility: Universtiy of Vermont
state: Vermont
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic Cancer Care & Research Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and Medical College of Wisconsin
state: Wisconsin
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Jerusalem
country: Israel
facility: Shaare Tzedek Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center, Department of Oncology
city: Nagoya
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Tōon
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Myagi
city: Tokorozawa
country: Japan
facility: National Defense Medical College Hospital
state: Saitama
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto
country: Japan
facility: Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Kraków
country: Poland
facility: Centrum Badan Klinicznych Jagiellonskiego Centrum Innowacji
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
city: Poznań
country: Poland
facility: MedPolonia Sp. z o.o.
city: Barcelona
country: Spain
facility: Parc Taulí Hospital Universitari Edifici Santa Fe, Planta 0, Sala de recerca 3
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia Edificio Onkologikoa- Planta baja, Sala de Ensayos Clinicos
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon Módulo prefabricado Oncología, Planta Baja
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid Unidad de ensayos Clinicos
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos.
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío Servicio Oncología Médica. Ensayos Clínicos. Edificio CDCA
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología Médica (IVO
city: Valencia
country: Spain
facility: Consorcio Hospitalario General Universitario de Valencia Servicio de Oncología Médica - Unidad de Investigación
Study officials:
References:
citation: 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.