Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients (STELLAR)

January 19, 2022 updated by: Orbus Therapeutics, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

343

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Flemish Brabant
      • Leuven, Flemish Brabant, Belgium, 3000
        • Universitair Ziekenhuis Leuven
    • Namur
      • Yvoir, Namur, Belgium, 5530
        • Cliniques Universitaires UCL de Mont-Godinne
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Center
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
      • Toronto, Ontario, Canada, M5G2M9
        • Princess Margaret Cancer Center
    • Quebec
      • Montréal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital
  • France
      • Angers, France, 49055
        • Institut de Cancérologie de l'Ouest - Angers
      • Brest, France, 29200
        • CHRU de Brest
      • Bron, France, 69500
        • Hôpital Pierre Wertheimer - Hospices Civils de Lyon
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Dijon, France, 21000
        • Centre Georges François Leclerc
      • Lille, France, 59037
        • Hôpital Roger Salengro
      • Marseille, France, 13005
        • Hopital de la Timone
      • Paris, France, 75013
        • Hôpital Universitaire Pitié Salpêtrière
  • Germany
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf
    • Bayern
      • Regensburg, Bayern, Germany, 93053
        • Klinik und Poliklinik für Neurologie der Universität Regensburg
    • Nordrhein-Westfalen
      • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
        • Heinrich-Heine-Universitat Duesseldorf
      • Essen, Nordrhein-Westfalen, Germany, 45147
        • Universitätsklinikum Essen
  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS - Instituto Neurologico Carlo Besta
      • Padova, Italy
        • Istituto Oncologico Veneto
      • Torino, Italy, 10126
        • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Universitair Medisch Centrum Utrecht
    • Noord-Brabant
      • Tilburg, Noord-Brabant, Netherlands, 5022 GC
        • Sint Elisabeth Ziekenhuis
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1081 HV
        • Vrije Universiteit Medisch Centrum (Vumc)
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3075 EA
        • Erasmus Medisch Centrum Daniel Den Hoed
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • University Hospitals Birmingham NHS Foundation Trust
      • Edinburgh, United Kingdom, EH4 2XU
        • Edinburgh Cancer Centre - Western General Hospital
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Guy's Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35401
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Saint Joseph's Hospital and Medical Center
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center
      • Redwood City, California, United States, 94063
        • Kaiser Permanente Center
      • Sacramento, California, United States, 95825
        • Kaiser Permanente
      • San Diego, California, United States, 92093
        • UCSD Moores Cancer Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco Medical Center
      • Santa Monica, California, United States, 90404
        • John Wayne Cancer Institute
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Florida
      • Tampa, Florida, United States, 33612
        • University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute
      • Atlanta, Georgia, United States, 30309
        • Piedmont Physicians Neuro-Oncology
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Warrenville, Illinois, United States, 60055
        • Northwestern Medicine CDH Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Chandler Medical Center
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute - Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Sciences Center New Orleans
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Center for Cancer Medicine and Blood Disorders
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute, Brigham and Women's Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Minnesota
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Cancer Institute
      • Kansas City, Missouri, United States, 64132
        • HCA Midwest Division
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • New Jersey
      • Edison, New Jersey, United States, 08820
        • JFK Medical Center
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • Columbia University Medical Center, The Neurological Institute
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina - Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic, Richard E. Jacobs Health Center
      • Columbus, Ohio, United States, 43214
        • OhioHealth Research and Innovation Institute
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Brain & Spine Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina, Hollings Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology Austin Brain Tumor Center
      • Dallas, Texas, United States, 75246
        • Neuro-Oncology Associates
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Health Services

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eflornithine + Lomustine
Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks
Drug: Eflornithine
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule
Other Names:
  • DFMO
Drug: Lomustine
Lomustine 90 mg/m2 administered orally once every 6 weeks
Other Names:
  • CCNU
  • CeeNU
  • Gleostine
Drug: Lomustine
Lomustine 110 mg/m2 administered orally once every 6 weeks
Other Names:
  • CCNU
  • CeeNU
  • Gleostine
Active Comparator: Lomustine
Lomustine dosed every 6 weeks
Drug: Lomustine
Lomustine 90 mg/m2 administered orally once every 6 weeks
Other Names:
  • CCNU
  • CeeNU
  • Gleostine
Drug: Lomustine
Lomustine 110 mg/m2 administered orally once every 6 weeks
Other Names:
  • CCNU
  • CeeNU
  • Gleostine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 4 years
4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival (PFS)
Time Frame: 4 years
4 years
Objective response rate (ORR)
Time Frame: 4 years
4 years

Other Outcome Measures

Outcome Measure
Time Frame
Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria
Time Frame: 4 years
4 years
OS rate at 18 months (OS-18)
Time Frame: 18 months
18 months
Relevance of OS, PFS, ORR, and CBR to commonly used molecular/genetic biomarkers obtained from most recent pre-study tumor samples
Time Frame: 4 years
4 years
Pharmacokinetic Analysis - Maximum concentrations (Cmax) of eflornithine in plasma will be determined.
Time Frame: 1 Month
1 Month
PK - Area under the curve (AUC) of eflornithine in plasma will be determined.
Time Frame: 1 Month
1 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Orbus Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2016

Primary Completion (Anticipated)

June 1, 2023

Study Completion (Anticipated)

June 1, 2023

Study Registration Dates

First Submitted

June 3, 2016

First Submitted That Met QC Criteria

June 7, 2016

First Posted (Estimate)

June 10, 2016

Study Record Updates

Last Update Posted (Actual)

January 21, 2022

Last Update Submitted That Met QC Criteria

January 19, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OT-15-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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