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

Phase 3

• Conditions: Anaplastic Astrocytoma; Recurrent Anaplastic Astrocytoma
• Interventions: Drug: Eflornithine; Drug: Lomustine

• Registration Number: NCT02796261
• Lead Sponsor: Orbus Therapeutics, Inc.

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 Timeline

• Study First Submitted: 2016-06-03
• Study First Submitted QC: 2016-06-07
• Study First Posted: 2016-06-10
• Study Start: 2016-07
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-19
• Last Update Posted: 2022-01-21
• Primary Completion: 2023-06
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 343

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Overall survival	4 years

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	4 years
Objective response rate (ORR)	4 years

Trial Locations

Locations (78)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Saint Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

Kaiser Permanente; 🇺🇸 Sacramento, California, United States

University of Southern California Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

University of California Irvine Medical Center; 🇺🇸 Orange, California, United States

Kaiser Permanente Center; 🇺🇸 Redwood City, California, 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

University of Colorado; 🇺🇸 Aurora, Colorado, United States

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