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

Orbus Therapeutics

Status and phase: Unknown; Phase 3

Conditions: Recurrent Anaplastic Astrocytoma; Anaplastic Astrocytoma

Treatments: Drug: Eflornithine; Drug: Lomustine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02796261

OT-15-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 343 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

343 participants in 2 patient groups

Eflornithine + Lomustine

Experimental group

Description:

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

Treatment:

Drug: Lomustine

Drug: Lomustine

Drug: Eflornithine

Lomustine

Active Comparator group

Description:

Lomustine dosed every 6 weeks

Treatment:

Drug: Lomustine

Drug: Lomustine