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

NCT ID: NCT00473408

Last Updated: 2016-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

1 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-03-31

Study Completion Date

2011-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Anaplastic Astrocytoma Glioblastoma Multiforme Tumor Angiogenesis

Keywords

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Glioma DCE-MRI Angiogenesis Cancer stem cells Tumor vasculature

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Functional MRI (DCE-MRI)

MRI examination with i.v. gadolinium contrast to assess blood perfusion in remaining tumor tissue.

Intervention Type DEVICE

Blood sample

See protocol.

Intervention Type PROCEDURE

Tumor sample

See protocol.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bergen

OTHER

Sponsor Role collaborator

Haukeland University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Hans Petter Eikesdal

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hans Petter Eikesdal, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway

Locations

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Dept. of Oncology & Dept. of Radiology, Haukeland University Hospital

Bergen, Norway, Hordaland, Norway

Site Status

Countries

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Norway

References

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Cao Y, Sundgren PC, Tsien CI, Chenevert TT, Junck L. Physiologic and metabolic magnetic resonance imaging in gliomas. J Clin Oncol. 2006 Mar 10;24(8):1228-35. doi: 10.1200/JCO.2005.04.7233.

Reference Type BACKGROUND
PMID: 16525177 (View on PubMed)

Morgan B, Thomas AL, Drevs J, Hennig J, Buchert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L, Mietlowski W, Fuxuis S, Unger C, O'Byrne K, Henry A, Cherryman GR, Laurent D, Dugan M, Marme D, Steward WP. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol. 2003 Nov 1;21(21):3955-64. doi: 10.1200/JCO.2003.08.092. Epub 2003 Sep 29.

Reference Type BACKGROUND
PMID: 14517187 (View on PubMed)

Mancuso P, Rabascio C, Bertolini F. Strategies to investigate circulating endothelial cells in cancer. Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):503-6. doi: 10.1159/000083853.

Reference Type BACKGROUND
PMID: 15692268 (View on PubMed)

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004 Nov 18;432(7015):396-401. doi: 10.1038/nature03128.

Reference Type BACKGROUND
PMID: 15549107 (View on PubMed)

Other Identifiers

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REK ID: 202.06

Identifier Type: REGISTRY

Identifier Source: secondary_id

15437

Identifier Type: -

Identifier Source: org_study_id