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

NCT02796261 | Unknown Phase 3 DMC

• 1 other identifier: OT-15-001
• Study Type: interventional
• Target: 343
• Locations: 8 countries
• Sites: 79

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  4 years

Secondary Outcomes (2)

• Progression-free survival (PFS)

  4 years

• Objective response rate (ORR)

  4 years

Other Outcomes (5)

• Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria

  4 years

• OS rate at 18 months (OS-18)

  18 months

• Relevance of OS, PFS, ORR, and CBR to commonly used molecular/genetic biomarkers obtained from most recent pre-study tumor samples

  4 years

Study Arms (2)

Eflornithine + Lomustine

EXPERIMENTAL

Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks

Drug: Eflornithine; Drug: Lomustine

Lomustine

ACTIVE COMPARATOR

Lomustine dosed every 6 weeks

Drug: Lomustine

Interventions

Eflornithine DRUG

Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule

Also known as: DFMO

Eflornithine + Lomustine

Lomustine DRUG

Lomustine 90 mg/m2 administered orally once every 6 weeks

Also known as: CCNU, CeeNU, Gleostine

Eflornithine + Lomustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Orbus Therapeutics, Inc.: lead

Study Sites (79)

University of Alabama at Birmingham

Birmingham, Alabama, 35401, United States

Location

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Kaiser Permanente Center

Redwood City, California, 94063, United States

Location

Kaiser Permanente

Sacramento, California, 95825, United States

Location

UCSD Moores Cancer Center

San Diego, California, 92093, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Piedmont Physicians Neuro-Oncology

Atlanta, Georgia, 30309, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Medicine CDH Cancer Center

Warrenville, Illinois, 60055, United States

Location

The University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute - Louisville

Louisville, Kentucky, 40202, United States

Location

Louisiana State University Health Sciences Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Maine Center for Cancer Medicine and Blood Disorders

Scarborough, Maine, 04074, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute, Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

Location

HCA Midwest Division

Kansas City, Missouri, 64132, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

JFK Medical Center

Edison, New Jersey, 08820, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Columbia University Medical Center, The Neurological Institute

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic, Richard E. Jacobs Health Center

Cleveland, Ohio, 44195, United States

Location

OhioHealth Research and Innovation Institute

Columbus, Ohio, 43214, United States

Location

Providence Brain & Spine Institute

Portland, Oregon, 97225, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Texas Oncology Austin Brain Tumor Center

Austin, Texas, 78705, United States

Location

Neuro-Oncology Associates

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Swedish Health Services

Seattle, Washington, 98122, United States

Location

Universitair Ziekenhuis Leuven

Leuven, Flemish Brabant, 3000, Belgium

Location

Cliniques Universitaires UCL De Mont-Godinne

Yvoir, Namur, 5530, Belgium

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G2M9, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Institut de Cancerologie de l'Ouest - Angers

Angers, 49055, France

Location

CHRU de Brest

Brest, 29200, France

Location

Hôpital Pierre Wertheimer - Hospices Civils de Lyon

Bron, 69500, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

Hôpital Roger Salengro

Lille, 59037, France

Location

Hôpital de la Timone

Marseille, 13005, France

Location

Hôpital Universitaire Pitié Salpêtrière

Paris, 75013, France

Location

Klinik und Poliklinik fur Neurologie der Universitat Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Heinrich-Heine-Universitat Duesseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Fondazione IRCCS - Instituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette

Torino, 10126, Italy

Location

Sint Elisabeth Ziekenhuis

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Vrije Universiteit Medisch Centrum (VUMC)

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Erasmus Medisch Centrum Daniel den Hoed

Rotterdam, South Holland, 3075 EA, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Edinburgh Cancer Centre - Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Colman H, Lombardi G, Wong ET, Walbert T, Eoli M, Lassman AB, Peereboom DM, Kizilbash SH, Kamiya-Matsuoka C, Pitz MW, Strowd RE, Desjardins A, Kumthekar P, Mason W, Pellerino A, Soffietti R, Butowski N, Forsyth PA, Hamza MA, Hau P, Lallana E, Nabors B, Piccioni D, Uhlmann EJ, Welsh LC, Wen PY, Dietrich J, Wang C, Levin VA. STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma. J Clin Oncol. 2025 Dec 1:JCO2501204. doi: 10.1200/JCO-25-01204. Online ahead of print.

  PMID: 41325560 DERIVED

MeSH Terms

Conditions

Astrocytoma; Glioma; Brain Neoplasms

Interventions

Eflornithine; Lomustine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 10, 2016
• Study Start: July 1, 2016
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: January 21, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); IT (3); DE (4); US (47); NL (4); FR (8); BE (2); CA (6)