NCT02974621

Cediranib Maleate and Olaparib Compared to Bevacizumab in Treating Patients With Recurrent Glioblastoma

A Randomized Phase 2 Trial of Cediranib and Olaparib Compared to Bevacizumab in Patients With Recurrent Glioblastoma Who Have Not Received Prior VEGF Therapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial studies how well cediranib maleate and olaparib work compared to bevacizumab in treating patients with glioblastoma that has come back (recurrent). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. To compare the antitumor activity of cediranib maleate (cediranib)/olaparib versus reference bevacizumab monotherapy, as measured by progression-free survival at 6 months (PF6), in patients with recurrent glioblastoma (GBM). SECONDARY OBJECTIVES: I. To compare overall survival (OS), progression free survival (PFS) and objective response (ORR) in patients with recurrent GBM treated with cediranib/olaparib versus bevacizumab. II. To assess the safety of the combination of olaparib and cediranib in patients with recurrent GBM. III. To evaluate the association of blood based biomarkers involved with angiogenesis using the Biomarker Review Committee-approved Plasma Angiome Panel (bFGF, Ang-1, Ang-2, Tie-2, SDF1-alpha, Collagen IV, PlGF, sVEGFR1, sVEGFR2, VEGF, Il-1beta, Il-6, Il-8, TNF-alpha, CAIX) with the clinical activity of cediranib/olaparib. IV. To evaluate the association of tissue biomarkers involved with deoxyribonucleic acid (DNA) repair using the Biomarker Review Committee-approved BROCA panel with the clinical activity of cediranib/olaparib. V. To identify genomic alteration by whole exome sequencing in GBM tumor specimens that correlate with the clinical activity of cediranib/olaparib. VI. To evaluate the association of magnetic resonance imaging (MRI) imaging parameters (tumor perfusion and oxygenation, brain tumor cellularity) with the biological response of cediranib/olaparib. VII. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. VIII. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive olaparib orally (PO) twice daily (BID) and cediranib maleate PO once daily (QD) on days 1-28. ARM B: Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks. In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then periodically for 3 years.

Conditions

• Recurrent Glioblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
DRUG	Cediranib	Given PO
DRUG	Cediranib Maleate	Given PO
DRUG	Olaparib	Given PO

Timeline

• Start date: 2017-12-07
• Primary completion: 2022-12-31
• Completion: 2026-07-17
• First posted: 2016-11-28
• Last updated: 2025-08-03
• Results posted: 2024-02-02

Locations

27 sites across 1 country: United States

Regulatory

• FDA-regulated drug study