Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

NCT00662506 | Completed Phase 1

• 7 other identifiers: NCI-2009-00267MGH-07-344PHS 398/2590CDR00005937178030P30CA006516R01CA129371
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial is studying the side effects and best dose of cediranib to see how well it works when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cediranib together with temozolomide and radiation therapy may kill more tumor cells.

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (Phase II)

  The fraction of patients alive and free of disease progression after the MRI scan scheduled. This fraction will be compared, using a one sample, two-sided exact binomial test, to 50% progression-free survival (PFS). For safety assessment, the study will be powered to ensure at least 85% chance of observing a serious adverse event, if the probability of such an event on treatment were \>=5%.

  At day 218

• Safety profile and optimal dose of cediranib during chemoradiotherapy (Phase I)

  A dose-limiting toxicity of cediranib is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/temozolomide and occurs following the first dose of cediranib in the chemoradiation.

  Up to 30 days after the last dose

Secondary Outcomes (3)

• Blood biomarkers (Phase II)

  Up to 1 year

• MRI parameters (Phase II)

  Up to 48 weeks

• Tumor biomarkers (Phase II)

  At baseline

Study Arms (1)

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

EXPERIMENTAL

See Detailed Description

Drug: Cediranib Maleate; Procedure: Diffusion Tensor Imaging; Procedure: Diffusion Weighted Imaging; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Radiation: Fludeoxyglucose F-18; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Procedure: Perfusion Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Temozolomide

Interventions

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Diffusion Tensor Imaging PROCEDURE

Undergo DTI

Also known as: DTI

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Diffusion Weighted Imaging PROCEDURE

Undergo T1 weighted DCE-MRI

Also known as: Diffusion Weighted MRI, Diffusion-Weighted Magnetic Resonance Imaging, Diffusion-Weighted MR Imaging, Diffusion-Weighted MRI, DWI, DWI MRI, DWI-MRI, MR Diffusion-Weighted Imaging

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging PROCEDURE

Undergo DCE-MRI

Also known as: DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Fludeoxyglucose F-18 RADIATION

Undergo 18 FDG PET

Also known as: 18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Perfusion Magnetic Resonance Imaging PROCEDURE

Undergo PWI

Also known as: magnetic resonance perfusion imaging

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Positron Emission Tomography PROCEDURE

Undergo 18 F FDG-PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed glioblastoma
• Newly diagnosed disease
• Scheduled to receive standard post-surgical (i.e., biopsy or resection) temozolomide and radiotherapy
• Must have residual, contrast-enhancing tumor (≥ 1 centimeter in ≥ 1 dimension)
• Patients must be maintained on a stable corticosteroid regimen for 5 days prior to their baseline scan and for 5 days prior to their first vascular MRI; the dose of steroids should remain the same during the baseline vascular MRIs
• Archival tumor tissue available for molecular analysis
• No intratumoral hemorrhage or peritumoral hemorrhage by MRI
• Karnofsky performance status 60-100%
• Leukocytes ≥ 3,000/mcl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 8 g/dL
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (4)

• Hoebel KV, Bridge CP, Ahmed S, Akintola O, Chung C, Huang RY, Johnson JM, Kim A, Ly KI, Chang K, Patel J, Pinho M, Batchelor TT, Rosen BR, Gerstner ER, Kalpathy-Cramer J. Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation. Radiol Artif Intell. 2024 Jan;6(1):e220231. doi: 10.1148/ryai.220231.

  PMID: 38197800 DERIVED

• Hoebel KV, Patel JB, Beers AL, Chang K, Singh P, Brown JM, Pinho MC, Batchelor TT, Gerstner ER, Rosen BR, Kalpathy-Cramer J. Radiomics Repeatability Pitfalls in a Scan-Rescan MRI Study of Glioblastoma. Radiol Artif Intell. 2020 Dec 16;3(1):e190199. doi: 10.1148/ryai.2020190199. eCollection 2021 Jan.

  PMID: 33842889 DERIVED

• Emblem KE, Farrar CT, Gerstner ER, Batchelor TT, Borra RJ, Rosen BR, Sorensen AG, Jain RK. Vessel caliber--a potential MRI biomarker of tumour response in clinical trials. Nat Rev Clin Oncol. 2014 Oct;11(10):566-84. doi: 10.1038/nrclinonc.2014.126. Epub 2014 Aug 12.

  PMID: 25113840 DERIVED

• Pinho MC, Polaskova P, Kalpathy-Cramer J, Jennings D, Emblem KE, Jain RK, Rosen BR, Wen PY, Sorensen AG, Batchelor TT, Gerstner ER. Low incidence of pseudoprogression by imaging in newly diagnosed glioblastoma patients treated with cediranib in combination with chemoradiation. Oncologist. 2014 Jan;19(1):75-81. doi: 10.1634/theoncologist.2013-0101. Epub 2013 Dec 5.

  PMID: 24309981 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

cediranib; Diffusion Tensor Imaging; Fluorodeoxyglucose F18; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Tomography; Diagnostic Techniques, Neurological; Investigative Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Elizabeth R Gerstner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 21, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 6, 2023

Record last verified: 2017-09

Locations

US (2)