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

December 5, 2016 updated by: Hans Petter Eikesdal, Haukeland University Hospital
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
    • Hordaland
      • Bergen, Norway, Hordaland, Norway, 5021
        • Dept. of Oncology & Dept. of Radiology, Haukeland University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Haukeland University Hospital

Collaborators

University of Bergen

Investigators

  • Principal Investigator: Hans Petter Eikesdal, MD PhD, Institute of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

May 1, 2007

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

May 14, 2007

First Submitted That Met QC Criteria

May 14, 2007

First Posted (Estimate)

May 15, 2007

Study Record Updates

Last Update Posted (Estimate)

December 6, 2016

Last Update Submitted That Met QC Criteria

December 5, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15437
  • REK ID: 202.06 (Registry Identifier: Regional Ethics Committee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Only one patient was included before the study was terminated.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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