Re-irradiation of High Grade Gliomas: a Quality of Life Study

May 11, 2015 updated by: Maastricht Radiation Oncology
Patients with a high grade glioma have an increasing overall survival and progression free survival after initial treatment. Because of a better performance status these patients are more often eligible for re-treatment with for example radiotherapy. However, to date only a few prospective studies on re-irradiation of gliomas exist and very little is known about the effects of re-irradiation on quality of life and cognition. This trial is designed to longitudinally establish the effects of re-irradiation on quality of life, cognition and physical performance in patients with a high grade glioma. Based on the currently available information the investigators hypothesize that quality of life after re-irradiation can be kept stable until further tumour progression.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Current treatment regimes, with the addition of temozolomide, have improved progression-free survival as well as overall survival for patients with a high grade glioma. The median overall survival (MOS) for patients with a glioblastoma (GBM) is 14.6 months, with a progression free survival (PFS) of 6.9 months.

Due to longer survival and a better performance status, patients often reach a point at which re-treatment is feasible. Treatment options for recurrent glioblastoma and anaplastic glioma can include surgery, chemotherapy and re-irradiation. Re-irradiation of patients with recurrent high grade glioma is slowly becoming standard of care. It provides a comparable overall survival to palliative chemotherapy. In case of GBM there is a median time to progression after treatment of 20-27 weeks and a MOS of 26 to 60 weeks.

Patients with tumor recurrence have a significantly worse quality of life compared to patients without recurrence at the same follow-up. They experience significantly more problems with physical functioning (e.g. motor dysfunction, weakness of legs, visual disorders), work or other daily activities, mental health (e.g. future uncertainty) and general health.

With regard to re-irradiation, current available data is mostly provided by retrospective studies which often lack solid quality of life data. Endpoints include e.g. performance status, clinical (neurological) status and decreased steroid requirement after treatment. These endpoints are however inadequate to determine quality of life accurately.

Several studies have used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) and the brain cancer module (QLQ-BN20) scales to assess quality of life. The latter consists of 20 items including visual disorder, motor dysfunction, various disease symptoms, treatment toxicity and future uncertainty. A change of 10 points or more on these scales can be considered clinically relevant.

To date only Ernst-Stecken and colleagues have used the EORTC QLQ-C30 to prospectively evaluate the quality of life in patients with a recurrent malignant glioma after radiotherapy. In this study patients were treated with hypofractionation. The quality of life questionnaire score could be kept stable in two thirds of patients with a median follow-up of 9 months. They conclude that hypofractionated stereotactic radiotherapy is an effective treatment that helps to maintain quality of life for an acceptable period, comparable to the results found with chemotherapeutic regimes.

In patients with glioma, the tumor, radiotherapy as well as chemotherapy can disrupt cognitive function. Cognitive functioning can be evaluated by a cognitive screening instrument and/or comprehensive neuropsychological test batteries. The most well-known and convenient screening instrument is the Mini Mental-State Examination (MMSE). However, the MMSE is developed to assess dementia and does not include items related to executive function. As such, the MMSE is insufficient to assess frontal-subcortical network dysfunction associated with cognitive damage after irradiation. More sensitive cognitive tests should be administered to determine the effects of re-irradiation on cognition. There is however still little consensus on which test should be used. Although comprehensive neuropsychological test batteries are most sensitive, a brief cognitive screening is preferable in the present setting. For this trial, the investigators intend to use a number of relevant standard tests including the Hopkins Verbal Learning Test-Revised (HVLT-R, the Trail Making Test and Controlled Oral Word Association (COWA) as suggested by the Radiation Therapy Oncology Group (RTOG). The Stroop colour-word test (Stroop) is added to the battery in order to assess visual attention.

Physical functioning has a major impact on quality of life in patients with cancer. A number of studies have investigated the effects of exercise on physical functioning. They have shown, predominantly in patients with breast cancer, that exercise has beneficial effects on health and well-being. Physical performance can be measured by several means. The hand grip strength (HGS) test has been validated in previous studies for the evaluation of general health status. This test is performed with the Jamar hand dynamometer which displays hand strength in kilograms. By comparing data after re-irradiation to the data collected before the treatment the amount of muscle strength loss can be determined.

Another method of measuring physical performance is by analyzing fatigue. This is a very common symptom in cancer patients and negatively influences their quality of life. Fatigue in patients with cancer can be determined with the use of both the EORTC QLQ-C30 and the more specific Fatigue Questionnaire (EORTC QLQ-FA13).

Study Type

Observational

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

  • Netherlands
      • Maastricht, Netherlands, 6229 ET
        • Maastricht Radiation Oncology

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

Probability Sample

Study Population

The study population will consist of subjects with a histologically proven high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme) at primary diagnosis, who are now eligible for re-irradation because of a recurrence.

Description

Inclusion Criteria:

  • Histologically proven high-grade glioma anaplastic astrocytoma or glioblastoma
  • Age ≥ 18 years
  • WHO performance status ≤ 2
  • Scheduled for re-irradiation of a high grade glioma
  • The patient is willing and capable to comply with study procedure

Exclusion Criteria:

• Life expectancy < 3 months

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Re-irradiation, high grade glioma
EORTC QLQ-C30 EORTC QLQ-BN20 Hopkins Verbal Learning Test-Revised (HVLT-R) Trail Making Test (TMT) Stroop color-word test Controlled oral word association test (COWA) Jamar hand dynamometer EORTC QLQ- FA13 Short Form health survey (SF-36)
Other: EORTC QLQ-C30
The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It is supplemented by disease specific modules for e.g. Breast, Lung, Head & Neck, Oesophageal, Ovarian, Gastric, Cervical cancer, Multiple Myeloma, Oesophago-Gastric, Prostate, Colorectal Liver Metastases, Colorectal and Brain cancer which are distributed from the EORTC Quality of Life Department. Other disease specific modules are under development but not yet validated.
Other: EORTC QLQ-BN20
The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It is supplemented by disease specific modules for e.g. Breast, Lung, Head & Neck, Oesophageal, Ovarian, Gastric, Cervical cancer, Multiple Myeloma, Oesophago-Gastric, Prostate, Colorectal Liver Metastases, Colorectal and Brain cancer which are distributed from the EORTC Quality of Life Department. Other disease specific modules are under development but not yet validated.
Other: Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R is a cognitive test to assess verbal learning and memory.
Other: Stroop color-word test
The Stroop Color and Word Test is a brief five minute test which is used to assess brain dysfunction, cognition, and psychopathology.
Other: Controlled oral word association test (COWA)
The COWA is a measure of verbal fluency that requires expressive language and executive functions.
Other: Jamar hand dynamometer
The Jamar hand dynamometer is a screening instrument that is used to assess grip strength.
Other: EORTC QLQ- FA13
The Fatigue Questionnaire (QLQ-FA13) is a 13-item questionnaire to assess fatigue in patients with cancer. It is meant to be used in conjunction with the EORTC QLQ-C30
Other: Trail Making Test (TMT)
The TMT The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in the palliative effect of re-irradiation in patients with a high grade glioma, defined by quality-of-life parameters
Time Frame: baseline, 6-8weeks, 12 weeks, 18-20 weeks, 30-32 weeks

These Quality of life parameters include:

  • The change in the EORTC QLQ-C30 score from baseline to endpoint
  • The change in the EORTC QLQ-BN20 score from baseline to endpoint
  • The change in the EORTC QLQ-FA13 score from baseline to endpoint
  • The change in cognition from baseline to endpoint as measured by the HVLT-R, the TMT, the Stroop-test and the COWA
  • The change in grip strength from baseline to endpoint
baseline, 6-8weeks, 12 weeks, 18-20 weeks, 30-32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival of patients with glioblastoma and anaplastic glioma after re-irradiation
Time Frame: 6 months after the last patient is included
- Months from the start of re-irradiation to death
6 months after the last patient is included
Progression free survival of patients with glioblastoma and anaplastic glioma after re-irradiation
Time Frame: 6 months after the last patient is included
- Months from the start of re-irradiation to tumorprogression
6 months after the last patient is included

Collaborators and Investigators

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

Sponsor

Maastricht Radiation Oncology

Investigators

  • Principal Investigator: Brigitta Baumert, MD, MBA, Maastro Clinic, The Netherlands

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, 2013

Primary Completion (Anticipated)

March 1, 2015

Study Completion (Anticipated)

September 1, 2015

Study Registration Dates

First Submitted

October 12, 2012

First Submitted That Met QC Criteria

October 18, 2012

First Posted (Estimate)

October 22, 2012

Study Record Updates

Last Update Posted (Estimate)

May 12, 2015

Last Update Submitted That Met QC Criteria

May 11, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-01-25/01-intern-6810

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.

Clinical Trials on Glioblastoma Multiforme

Clinical Trials on EORTC QLQ-C30

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United States

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe