Clinical trial NCT02796261: Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients
Official title: A Randomized Phase 3 Open-Label Study To Evaluate the Efficacy and Safety of Eflornithine With Lomustine Compared to Lomustine Alone in Patients With AA That Progress/Recur After Irradiation and Adjuvant Temozolomide Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Anaplastic Astrocytoma
Recurrent Anaplastic Astrocytoma
Keywords: Anaplastic Astrocytoma
Grade 3 Glioma
Glioma
Eflornithine
Brain Cancer
Brain Tumor
Neuro-oncology
Progressive Anaplastic Astrocytoma
Recurrent Anaplastic Astrocytoma
Progressive Glioma
Recurrent Glioma
Malignant Glioma
Progressive Brain Tumor
Recurrent Brain Tumor
Lead sponsor: Orbus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-10
Enrollment: 343
Sex: ALL
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 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.

Eligibility criteria: Inclusion Criteria:

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:

  1. Gd-contrast lesion margins are not clearly defined,
  2. Gd-contrast lesions are only measurable in one dimension,
  3. Gd-contrast lesion has two perpendicular diameters less than 10 mm,
  4. Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less than 20 mm and lesion does not demonstrate central necrosis,
  5. 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.

Exclusion Criteria:

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.

Primary outcomes:
measure: Overall survival
timeFrame: 4 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 4 years
measure: Objective response rate (ORR)
timeFrame: 4 years
Other outcomes:
measure: Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria
timeFrame: 4 years
measure: OS rate at 18 months (OS-18)
timeFrame: 18 months
measure: Relevance of OS, PFS, ORR, and CBR to commonly used molecular/genetic biomarkers obtained from most recent pre-study tumor samples
timeFrame: 4 years
measure: Pharmacokinetic Analysis - Maximum concentrations (Cmax) of eflornithine in plasma will be determined.
timeFrame: 1 Month
measure: PK - Area under the curve (AUC) of eflornithine in plasma will be determined.
timeFrame: 1 Month
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Saint Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: San Diego
country: United States
facility: UCSD Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Tampa
country: United States
facility: University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Physicians Neuro-Oncology
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine CDH Cancer Center
state: Illinois
city: Iowa City
country: United States
facility: The University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute - Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center New Orleans
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute, Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Kansas City
country: United States
facility: HCA Midwest Division
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center, The Neurological Institute
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic, Richard E. Jacobs Health Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research and Innovation Institute
state: Ohio
city: Portland
country: United States
facility: Providence Brain & Spine Institute
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Austin Brain Tumor Center
state: Texas
city: Dallas
country: United States
facility: Neuro-Oncology Associates
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Flemish Brabant
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL De Mont-Godinne
state: Namur
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Angers
country: France
facility: Institut de Cancerologie de l'Ouest - Angers
city: Brest
country: France
facility: CHRU de Brest
city: Bron
country: France
facility: Hôpital Pierre Wertheimer - Hospices Civils de Lyon
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Hôpital Roger Salengro
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Hôpital Universitaire Pitié Salpêtrière
city: Regensburg
country: Germany
facility: Klinik und Poliklinik fur Neurologie der Universitat Regensburg
state: Bayern
city: Düsseldorf
country: Germany
facility: Heinrich-Heine-Universitat Duesseldorf
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Milano
country: Italy
facility: Fondazione IRCCS - Instituto Neurologico Carlo Besta
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette
city: Tilburg
country: Netherlands
facility: Sint Elisabeth Ziekenhuis
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum (VUMC)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum Daniel den Hoed
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre - Western General Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
References: