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

Sponsor
Orbus Therapeutics, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02796261
Collaborator
(none)
343
Enrollment
79
Locations
2
Arms
83
Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
343 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Jul 1, 2016
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

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

    		•
    Active Comparator: Lomustine

    Lomustine dosed every 6 weeks

    Drug: Lomustine
    Lomustine 110 mg/m2 administered orally once every 6 weeks
    Other Names:
  • CCNU
  • CeeNU
  • Gleostine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival [4 years]

    Secondary Outcome Measures

    1. Progression-free survival (PFS) [4 years]

    2. Objective response rate (ORR) [4 years]

    Other Outcome Measures

    1. Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria [4 years]

    2. OS rate at 18 months (OS-18) [18 months]

    3. Relevance of OS, PFS, ORR, and CBR to commonly used molecular/genetic biomarkers obtained from most recent pre-study tumor samples [4 years]

    4. Pharmacokinetic Analysis - Maximum concentrations (Cmax) of eflornithine in plasma will be determined. [1 Month]

    5. PK - Area under the curve (AUC) of eflornithine in plasma will be determined. [1 Month]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Orbus Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Orbus Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02796261
    Other Study ID Numbers:
    • OT-15-001
    First Posted:
    Jun 10, 2016
    Last Update Posted:
    Jan 21, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Orbus Therapeutics, Inc.
    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
    Additional relevant MeSH terms:
    Astrocytoma
    Recurrence
    Eflornithine
    Lomustine

    Study Results

    No Results Posted as of Jan 21, 2022