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Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
First Received: April 18, 2008   Last Updated: April 18, 2009   History of Changes
Sponsors and Collaborators: Massachusetts General Hospital
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00662506
  Purpose

RATIONALE: 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.

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: cediranib maleate
Drug: temozolomide
Genetic: proteomic profiling
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: diffusion tensor imaging
Procedure: diffusion-weighted magnetic resonance imaging
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Radiation: fludeoxyglucose F 18
Radiation: intensity-modulated radiation therapy
Phase I
Phase II

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy
MedlinePlus related topics: Cancer MRI Scans Radiation Therapy
Drug Information available for: Fluorodeoxyglucose F18 Temozolomide Cediranib
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

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

Primary Outcome Measures:
  • Safety profile and optimal dose of cediranib during chemoradiotherapy [ Designated as safety issue: Yes ]
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MRI parameters [ Designated as safety issue: No ]
  • Blood biomarkers [ Designated as safety issue: No ]
  • Tumor biomarkers [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: April 2008
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  • No other concurrent chemotherapy agents, investigational agents, or biologic therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00662506

Locations
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Y. Wen, MD     617-632-2166     patrick_wen@dfci.harvard.edu    
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Clinical Trials Office - Massachusetts General Hospital     877-726-5130        
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Study Chair: Tracy Batchelor, MD, MPH Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Massachusetts General Hospital ( Tracy Batchelor )
Study ID Numbers: CDR0000593717, MGH-07-344
Study First Received: April 18, 2008
Last Updated: April 18, 2009
ClinicalTrials.gov Identifier: NCT00662506     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Adjuvants, Immunologic
Central Nervous System Neoplasms
Temozolomide
Neuroectodermal Tumors
Epilepsy
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Antineoplastic Agents, Alkylating
Glioma
Gliosarcoma
Alkylating Agents
Anticonvulsants
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Glioblastoma
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Nervous System Diseases
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Temozolomide
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Antineoplastic Agents, Alkylating
Glioma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009