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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00662506
First received: April 18, 2008
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Drug: cediranib maleate
Drug: temozolomide
Radiation: intensity-modulated radiation therapy
Radiation: fludeoxyglucose F 18
Procedure: perfusion-weighted magnetic resonance imaging
Procedure: diffusion tensor imaging
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Procedure: diffusion-weighted magnetic resonance imaging
Procedure: positron emission tomography
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of AZD2171 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma Not Taking Enzyme-Inducing Anti-Epileptic Drugs

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety profile and optimal dose of cediranib during chemoradiotherapy (Phase I) [ Time Frame: Up to 30 days after the last dose ] [ Designated as safety issue: Yes ]
    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.

  • Progression-free survival (Phase II) [ Time Frame: At day 218 ] [ Designated as safety issue: No ]
    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%.


Secondary Outcome Measures:
  • MRI parameters (Phase II) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    The comparisons of all MRI measurements will be against their day -1 values (baseline), using a 2-sided, paired Wilcoxon test (Hollander and Wolfe 1973).

  • Blood biomarkers (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Log-transformation is expected to yield approximately homogenous and symmetric standard errors, both for Poisson events and quantities obtained by assays with successive dilutions. We will plot the median levels and quartiles over time. First, we will compare on-study values to baseline, than we will test for an association between treatment time and markers, using a linear mixed effects model with log-transformed data and a spline function of time. The two-sided, paired t-test test will be powered to detect an effect-size of 0.5.

  • Tumor biomarkers (Phase II) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Exploratory analyses will be performed to determine if there is any correlation between the molecular/vascular phenotype of the tumor or quantitative measurements, we will use for this purpose ANOVA on log-transformed marker measurements. We will analyze changes in the measurements, and correlate biomarkers with clinical and radiographic response, similarly as for blood and urine biomarkers.


Estimated Enrollment: 40
Study Start Date: April 2008
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)
See Detailed Description
Drug: cediranib maleate
Given PO
Other Names:
  • AZD2171
  • Recentin
Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Radiation: fludeoxyglucose F 18
Undergo 18 FDG PET
Other Names:
  • 18FDG
  • FDG
Procedure: perfusion-weighted magnetic resonance imaging
Undergo PWI
Other Name: PW-MRI
Procedure: diffusion tensor imaging
Undergo DTI
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Undergo DCE-MRI
Other Name: DCE-MRI
Procedure: diffusion-weighted magnetic resonance imaging
Undergo T1 weighted DCE-MRI
Other Name: diffusion-weighted MRI
Procedure: positron emission tomography
Undergo 18 F FDG-PET
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Proteinuria ≤ 1+ on two consecutive dipsticks ≥ 7 days apart
  • Mini-mental status examination score ≥ 15
  • Must be able to tolerate MRI and must consent to participate in additional Vascular Imaging Procedures per protocol

    • CT scans cannot be substituted for MRI
  • Mean QTc ≤ 500 msec (with Bazett's correction) by electrocardiogram
  • No concurrent malignancy except curatively treated basal cell or squamous cell carcinoma skin cancer or carcinoma in situ of the cervix or breast

    • Patients with prior malignancies must be disease-free for ≥ 5 years
  • No history of familial long QT syndrome or other significant ECG abnormality
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Hypertension (e.g., blood pressure > 140/90 mm Hg)
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would preclude study compliance
  • No known coagulopathy that increases risk of bleeding
  • No history of clinically significant hemorrhages in the past
  • No New York Heart Association class III-IV heart disease
  • No condition requiring concurrent drugs or biologics with proarrhythmic potential
  • No other concurrent chemotherapy agents, investigational agents, or biologic therapy
  • No prior chemotherapy, radiotherapy, or any experimental therapy for this disease
  • No prior IV bevacizumab for any other medical condition
  • No prior carmustine implant (Gliadel Wafer)
  • No prior brachytherapy or radiosurgery for this disease
  • More than 30 days since prior and no other concurrent investigational agents or participation in an investigational therapeutic trial
  • At least 2 weeks since prior and no concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)

    • Concurrent non-EIAEDs allowed
  • No concurrent CYP450-inducing anticonvulsants
  • No concurrent anticoagulants (e.g., dalteparin, warfarin, or low-molecular weight heparin)

    • If patients require warfarin or other anticoagulants (e.g., low-molecular weight heparin) while on study, then patient may continue treatment
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent VEGF inhibitors
  • No concurrent pentamidine
  • No concurrent herbal or nontraditional medications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00662506

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Principal Investigator: Tracy Batchelor Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00662506     History of Changes
Other Study ID Numbers: NCI-2009-00267, NCI-2009-00267, MGH-07-344, R01CA129371, CDR0000593717, PHS 398/2590, 8030, R01CA129371, P30CA006516
Study First Received: April 18, 2008
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Cediranib
Fluorodeoxyglucose F18
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Radiopharmaceuticals
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on September 18, 2014