Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients
- Conditions
- Anaplastic AstrocytomaRecurrent Anaplastic Astrocytoma
- Interventions
- Registration Number
- NCT02796261
- Lead Sponsor
- Orbus Therapeutics, Inc.
- Brief Summary
The purpose of this study is to compare the efficacy and safety of eflornithine in combination with lomustine, compared to lomustine taken alone, in treating patients whose anaplastic astrocytoma has recurred/progressed after radiation and temozolomide chemotherapy.
- Detailed Description
This study will consist of 4 study periods of up to 50 months in total, consisting of:
Screening Period - A maximum screening duration of 4 weeks.
Treatment Period - Treatment Arm A up to 24 months; Treatment Arm B up to 12 months.
End of Treatment Visit - A minimum of 4 weeks post last treatment for both arms.
Follow-Up Period - Up to approximately 36 months, or until patient death.
A total of approximately 340 patients will be randomized in a 1:1 ratio to receive either eflornithine + lomustine or lomustine alone.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 343
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
-
Surgical or biopsy-proven diagnosis of WHO grade 3 AA.
-
First AA tumor progression or recurrence ≤ 6 months prior to randomization based on MRI using T2 hyperintesity, gadolinium (Gd)-contrast enhancement, or both. To avoid enrollment of patients with glioblastoma, patients with Gd-contrast enhancing tumors will be eligible if there is no necrosis seen on MRI and any of the following criteria is true:
- Gd-contrast lesion margins are not clearly defined,
- Gd-contrast lesions are only measurable in one dimension,
- Gd-contrast lesion has two perpendicular diameters less than 10 mm,
- Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less than 20 mm and lesion does not demonstrate central necrosis,
- Recent histopathological confirmation of WHO grade 3 AA
-
Received EBRT and temozolomide chemotherapy prior to first tumor progression or recurrence of WHO Grade 3 AA.
-
Completion of EBRT ≥ 6 months prior to randomization.
-
A patient whose AA tumor has progressed or recurred and has had another surgical resection prior to randomization will be eligible if a) pathology review confirms AA, and b) post-surgical MRI demonstrates measurable tumor on T2 FLAIR.
-
Karnofsky Performance Status (KPS) score of ≥ 70.
Patients who meet any of the following exclusion criteria are not eligible for study participation:
- MRI defining progression is consistent with a diagnosis of glioblastoma or radiation necrosis.
- Patients who are considered to be refractory to EBRT and temozolomide but who have not progressed.
- Prior systemic therapy for recurrence of AA.
- Presence of extracranial or leptomeningeal disease.
- Prior lomustine use.
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study.
- Pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eflornithine + Lomustine Eflornithine Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks Eflornithine + Lomustine Lomustine Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks Lomustine Lomustine Lomustine dosed every 6 weeks
- Primary Outcome Measures
Name Time Method Overall survival 4 years
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) 4 years Objective response rate (ORR) 4 years
Trial Locations
- Locations (78)
Montreal Neurological Institute and Hospital
🇨🇦Montréal, Quebec, Canada
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Hôpital de la Timone
🇫🇷Marseille, France
Klinik und Poliklinik fur Neurologie der Universitat Regensburg
🇩🇪Regensburg, Bayern, Germany
Heinrich-Heine-Universitat Duesseldorf
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Louisiana State University Health Sciences Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Hôpital Roger Salengro
🇫🇷Lille, France
Medical University of South Carolina, Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Tom Baker Cancer Center
🇨🇦Calgary, Alberta, Canada
JFK Medical Center
🇺🇸Edison, New Jersey, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Vrije Universiteit Medisch Centrum (VUMC)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Dana Farber Cancer Institute, Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Maine Center for Cancer Medicine and Blood Disorders
🇺🇸Scarborough, Maine, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Fondazione IRCCS - Instituto Neurologico Carlo Besta
🇮🇹Milano, Italy
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette
🇮🇹Torino, Italy
Sint Elisabeth Ziekenhuis
🇳🇱Tilburg, Noord-Brabant, Netherlands
Cliniques Universitaires UCL De Mont-Godinne
🇧🇪Yvoir, Namur, Belgium
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Providence Brain & Spine Institute
🇺🇸Portland, Oregon, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of Southern California Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Kaiser Permanente
🇺🇸Sacramento, California, United States
Piedmont Physicians Neuro-Oncology
🇺🇸Atlanta, Georgia, United States
UCSD Moores Cancer Center
🇺🇸San Diego, California, United States
Norton Cancer Institute - Louisville
🇺🇸Louisville, Kentucky, United States
The University of Iowa
🇺🇸Iowa City, Iowa, United States
The Cleveland Clinic, Richard E. Jacobs Health Center
🇺🇸Cleveland, Ohio, United States
Mayo Clinic Minnesota
🇺🇸Rochester, Minnesota, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Columbia University Medical Center, The Neurological Institute
🇺🇸New York, New York, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Swedish Health Services
🇺🇸Seattle, Washington, United States
Hôpital Universitaire Pitié Salpêtrière
🇫🇷Paris, France
Institut de Cancerologie de l'Ouest - Angers
🇫🇷Angers, France
CHRU de Brest
🇫🇷Brest, France
Edinburgh Cancer Centre - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Hôpital Pierre Wertheimer - Hospices Civils de Lyon
🇫🇷Bron, France
Erasmus Medisch Centrum Daniel den Hoed
🇳🇱Rotterdam, Zuid-Holland, Netherlands
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
HCA Midwest Division
🇺🇸Kansas City, Missouri, United States
Kaiser Permanente Center
🇺🇸Redwood City, California, United States
Northwestern Medicine CDH Cancer Center
🇺🇸Warrenville, Illinois, United States
OhioHealth Research and Innovation Institute
🇺🇸Columbus, Ohio, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Neuro-Oncology Associates
🇺🇸Dallas, Texas, United States
Texas Oncology Austin Brain Tumor Center
🇺🇸Austin, Texas, United States
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Flemish Brabant, Belgium
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Guy's Hospital
🇬🇧London, United Kingdom