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

• ClinicalTrials.gov Identifier: NCT02796261
• Recruitment Status: Active, not recruiting
• First Posted: June 10, 2016
• Last Update Posted: January 21, 2022
• Sponsor: Orbus Therapeutics, Inc.
• Information provided by (Responsible Party): Orbus Therapeutics, Inc.

Tracking Information

• First Submitted Date: June 3, 2016
• First Posted Date: June 10, 2016
• Last Update Posted Date: January 21, 2022
• Study Start Date: July 2016
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 7, 2016): Overall survival [ Time Frame: 4 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 7, 2016)

• Progression-free survival (PFS) [ Time Frame: 4 years ]
• Objective response rate (ORR) [ Time Frame: 4 years ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 7, 2016)

• Clinical benefit response (CBR) based on magnetic resonance imaging (MRI) criteria [ Time Frame: 4 years ]
• OS rate at 18 months (OS-18) [ Time Frame: 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 ]
• Pharmacokinetic Analysis - Maximum concentrations (Cmax) of eflornithine in plasma will be determined. [ Time Frame: 1 Month ]
• PK - Area under the curve (AUC) of eflornithine in plasma will be determined. [ Time Frame: 1 Month ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Anaplastic 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
  Other Name: 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

Study Arms

• Experimental: Eflornithine + Lomustine
  Eflornithine dosed on a 2 weeks on, 1 week off schedule + Lomustine dosed every 6 weeks
  Interventions:

  • Drug: Eflornithine
  • Drug: Lomustine
• Active Comparator: Lomustine
  Lomustine dosed every 6 weeks
  Intervention: Drug: Lomustine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 12, 2022): 343
• Original Estimated Enrollment (submitted: June 7, 2016): 280
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Germany, Italy, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT02796261
• Other Study ID Numbers: OT-15-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Orbus Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Orbus Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Orbus Therapeutics, Inc.
• Verification Date: January 2022