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

Anaplastic Astrocytoma Clinical Trial

— STELLAR  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02796261
• Other study ID #: OT-15-001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 2016
• Est. completion date: June 2023

Study information

• Verified date: January 2022
• Source: Orbus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 343
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• Recurrent Anaplastic Astrocytoma

Intervention

Drug:
• Eflornithine
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 week on, 1 week off schedule
• Lomustine
Lomustine 90 mg/m2 administered orally once every 6 weeks
• Lomustine
Lomustine 110 mg/m2 administered orally once every 6 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Orbus Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

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