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The Effect of Radiotherapy and Temozolomide on the Tumor Vasculature and Stem Cells in Human High-grade Astrocytomas (Gliomstudien)

This study has been terminated.
(Moved to another country, not possible to recruit from abroad.)
Sponsor:
Collaborator:
University of Bergen
Information provided by (Responsible Party):
Hans Petter Eikesdal, Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT00473408
First received: May 14, 2007
Last updated: November 18, 2011
Last verified: November 2011
  Purpose

The purpose of the current trial is to explore whether the standard treatment with radiotherapy and temozolomide affect the tumor vasculature in patients with high-grade astrocytomas. If vascular effects are identified, future clinical trials can be proposed wherein anti-angiogenic agents are added to increase patient survival.


Condition Intervention
Anaplastic Astrocytoma
Glioblastoma Multiforme
Tumor Angiogenesis
Device: Functional MRI (DCE-MRI)
Procedure: Blood sample
Procedure: Tumor sample

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Radiotherapy and Temozolomide on the Tumor Vasculature and Stem Cells in Human High-grade Astrocytomas

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Biospecimen Retention:   Samples With DNA

Tumor samples and blood samples are collected and frozen for future analysis for tumor vascularization and tumor stem cells.


Estimated Enrollment: 20
Study Start Date: March 2007
Study Completion Date: November 2011
Estimated Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: Functional MRI (DCE-MRI)
    MRI examination with i.v. gadolinium contrast to assess blood perfusion in remaining tumor tissue.
    Procedure: Blood sample
    n.a.
    Procedure: Tumor sample
    See protocol.
Detailed Description:

Today's standard treatment with radiotherapy and temozolomide yields a life expectancy of 1.5-3 years in patients with high-grade astrocytomas. Thus, there is a need for further therapeutic improvements in this patient population. The purpose of the current trial is to explore whether radiotherapy and temozolomide affect the tumor vasculature in patients with high-grade astrocytomas. If vascular effects are identified, future clinical trials can be proposed wherein anti-angiogenic agents are added to increase patient survival. Additionally, stem cells within malignant brain tumors is an important new area of research in this patient population, and investigations herein could contribute to identify new predictive markers and therapeutic targets.

Primary objective: To assess the vascular perfusion and permeability characteristics of high-grade astrocytomas (anaplastic astrocytoma and glioblastoma multiforme) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients receiving radiotherapy and temozolomide. Furthermore to assess whether therapy-induced changes in tumor perfusion is correlated with progression-free survival.

Secondary objectives:

  • Analyze circulating endothelial cells in the blood by flow cytometry to explore whether these cells can be used as an indirect estimate of angiogenesis in high-grade astrocytomas
  • Analyze tumor specimens from patients that have had their gliomas debulked before commencing therapy

    • immunostaining of the tumor vasculature to assess microvessel density
    • immunostaining for tumor stem cells
    • flow cytometric assessment of dissolved tumor tissue to look for tumor stem cells
  • Assess progression-free survival of all patients included in the study, in order to correlate the survival data with the above tissue sampling results.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients 18 years or older diagnosed and operated for high-grade astrocytoma.

Criteria

Inclusion Criteria:

  • Histologically confirmed primary high-grade astrocytoma, i.e. anaplastic astrocytoma or glioblastoma multiforme.
  • Have a WHO performance status 0-2 and be able to undergo outpatient treatment.
  • Age ≥18 years.
  • No pregnant or lactating patients can be included.
  • Patients must have radiographically documented measurable disease postoperatively. At least one tumor lesion must be unidimensionally measurable as follows:

    • Tumor lesion > 10 mm on conventional MRI scan, T1-weighted series, after intravenous (i.v.) gadolinium chelate contrast.
  • All diagnostic radiology studies must be performed within 28 days prior to registration.
  • Absence of conditions making MRI scans impossible;

    • Cardiac pacemaker
    • Other ferromagnetic metal implants not authorised for use in MRI such as some types of cerebral aneurysm clips
    • Serious claustrophobia
    • Obesity (> 300 lb., 140 Kg)
  • Patients who are receiving corticosteroids have to receive stable or decreasing doses for at least 14 days before entering the trial.
  • No prior chemotherapy for high-grade astrocytoma
  • Absence of opportunistic infections making temozolomide contraindicated.
  • Minimum required laboratory data:

    • Hematology:

      • Absolute granulocytes > 1.0 x 10^9/L
      • Platelets > 100 x 10^9/L
    • Biochemistry:

      • Bilirubin < 1.5 x upper normal limit
      • INR < 1.5
      • Serum creatinine <1.5 x upper normal limit
  • Adequate cognitive function in order to give informed consent.
  • Absence of any psychological, familial or sociological condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Before patient registration/randomization, written informed consent must be given according to national and local regulations.

Exclusion Criteria:

  • Lack of fulfillment of inclusion criteria.
  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: NCT00473408

Locations
Norway
Dept. of Oncology & Dept. of Radiology, Haukeland University Hospital
Bergen, Norway, Hordaland, Norway, 5021
Sponsors and Collaborators
Haukeland University Hospital
University of Bergen
Investigators
Principal Investigator: Hans Petter Eikesdal, MD PhD Institute of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway
  More Information

Publications:
Responsible Party: Hans Petter Eikesdal, MD PhD, Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT00473408     History of Changes
Other Study ID Numbers: 15437, REK ID: 202.06
Study First Received: May 14, 2007
Last Updated: November 18, 2011
Health Authority: Norway: Norwegian Social Science Data Services
Norway: Directorate of Health

Keywords provided by Haukeland University Hospital:
Glioma
DCE-MRI
Angiogenesis
Cancer stem cells
Tumor vasculature

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

ClinicalTrials.gov processed this record on November 20, 2014