AzTrials
AzTrials

Adult Diffuse AstrocytomaNCT01417507

Natural History of Brain Function, Quality of Life, and Seizure Control in Patients With Brain Tumor Who Have Undergone Surgery

An observational study of Adult Diffuse Astrocytoma and Adult Mixed Glioma, run by Radiation Therapy Oncology Group at 41 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This trial studies the natural history of brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery. Learning about brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery may help doctors learn more about the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cognitive assessment, magnetic resonance imaging and laboratory biomarker analysis
Type of treatment
Surgery or procedure
How many people
82 participants
Where
41 sitesin 2 countries
Study dates
Oct 2011to Dec 2014
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Central pathology-confirmed diagnosis of supratentorial grade II oligodendroglioma, astrocytome or mixed oligoastrocytoma prior to Step 2 registration. The patient must be within one of the following categories: Maximal safe resection with minimal residual disease defined as follows: * Removal of T2/FLAIR abnormalities thought to be primarily tumor, with a residual ≤ 2 cm maximal tumor diameter/T2 FLAIR abnormality on MRI to be done within 84 days postoperatively. * Patients who require a second surgery to obtain a maximal safe resection will be eligible if the second surgery is performed within 84 days of the inital diagnostic procedure. OR Age <40 (any extent of resection) OR Age <50, preoperative tumor diameter <4 cm (any extent of resection)

Who may be able to join

  • Central pathology confirmed diagnosis of supratentorial grade II oligodendroglioma, astrocytoma, or mixed oligoastrocytoma prior to step 2 registration
  • No multifocal disease, based upon the following minimum diagnostic work-up:
  • History/physical examination, including neurologic examination, within 84 days prior to step 2 registration
  • Brain MRI with and without contrast within 84 days prior to Step 2 registration (Note: MRI 70 days after surgery is preferred and highly encouraged)
  • The patient must be within one of the following categories:
  • Maximal safe resection with minimal residual disease defined as follows:
Show all 19Show fewer
  • Removal of T2/fluid-attenuated inversion recovery (FLAIR) abnormalities thought to be primarily tumor, with a residual ≤ 2 cm maximal tumor diameter/T2 FLAIR abnormality on MRI to be done within 84 days post-operatively
  • If there is > 2 cm post-operative residual T2/FLAIR abnormality and the neurosurgeon believes this represents edema and not primarily tumor, the neurosurgeon is encouraged to repeat imaging within the allowed study period (up to 84 days post-operatively) to confirm resolution of edema
  • MRI at the time of enrollment must document a ≤ 2 cm residual maximal tumor diameter/T2 FLAIR abnormality
  • Patients who required a second surgery to obtain a maximal safe resection will be eligible if the second surgery is performed within 84 days of the initial diagnostic procedure
  • Age < 40 (any extent of resection)
  • Age < 50 and preoperative tumor diameter < 4 cm (any extent of resection)
  • Karnofsky performance status ≥ 80%
  • No prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Must be able to undergo MRI of the brain with gadolinium
  • No plans for adjuvant radiotherapy or chemotherapy after surgery
  • No more than 84 days (12 weeks) since prior surgery
  • No brain tumor recurrence
  • No prior brain tumor surgery, radiation therapy and/or chemotherapy

Who cannot join

None listed.

Trial locations and contacts

41 sites in 2 countries.

41 sites in 2 countries

United States39 sites

  • Leeward Radiation Oncology Center

    ‘Ewa Beach, Hawaii, 96706

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Billings Clinic

    Billings, Montana, 59107-7000

  • The Kirklin Clinic at Acton Road

    Birmingham, Alabama, 35243

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • Evanston CCOP-NorthShore University HealthSystem

    Evanston, Illinois, 60201

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Cherry Tree Cancer Center

    Hanover, Pennsylvania, 17331

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • Hawaii Medical Center East

    Honolulu, Hawaii, 96817

  • Norton Health Care Pavilion - Downtown

    Louisville, Kentucky, 40202

  • Norton Suburban Hospital

    Louisville, Kentucky, 40207

  • Community Memorial Hospital

    Menomonee Falls, Wisconsin, 53051

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Providence Hospital

    Mobile, Alabama, 36608

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Florida Hospital

    Orlando, Florida, 32803

  • Radiation Therapy Oncology Group

    Philadelphia, Pennsylvania, 19103

  • Arizona Oncology Services Foundation

    Phoenix, Arizona, 85013

  • Arizona Oncology-Deer Valley Center

    Phoenix, Arizona, 85027

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Barnes West County Hospital

    St Louis, Missouri, 63141

  • Montefiore Medical Center

    The Bronx, New York, 10467-2490

  • Covenant Medical Center

    Waterloo, Iowa, 50702

  • Waukesha Memorial Hospital

    Waukesha, Wisconsin, 53188

  • York Hospital

    York, Pennsylvania, 17405

Other trials in United States

Canada2 sites

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • McGill University Department of Oncology

    Montreal, Quebec, H2W 1S6

Other trials in Canada

About this study

Official title: Natural History of Postoperative Cognitive Function, Quality of Life, and Seizure Control in Patients With Supratentorial Low-Risk Grade II Glioma

This trial studies the natural history of brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery. Learning about brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery may help doctors learn more about the disease and find better methods of treatment and on-going care.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if there is difference in the average changes of neurocognitive function (NCF) scores from baseline to the time of radiologic tumor progression or up to 5 years (whichever occurs first), between radiologically progressed and non-progressed patients.

SECONDARY OBJECTIVES:

  1. To determine if there is difference in the time to neurocognitive decline, as defined by the Reliable Change Index - Within subjects Standard Deviation (RCI-WSD), between radiologically progressed and non-progressed patients.

II. To evaluate NCF during the postoperative observational period of progression-free survival (PFS) and after radiological progression for a total time on study of 5 years.

III. To determine if the changes in cognitive functioning are an early warning biomarker for radiological progression.

IV. To explore the effect of salvage therapy on cognitive outcomes in patients who progress during the study period for up to 5 years.

  1. To evaluate quality-of-life (QOL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL-30 and QOL brain module (BCN20) and health utilities as measured by the European Quality of Life-5 Dimensions (EQ-5D), for a total time on study of 5 years.

VI. To evaluate seizure control for a total time on study of 5 years. VII. To evaluate molecular correlates of QOL, NCF, seizure control, and PFS. VIII. To characterize aberrant molecular pathways in low-grade gliomas (LGGs) and test the hypothesis that activation of signaling pathways will predict worse PFS and overall survival (OS).

IX. To explore the relationship between change in cognitive function and symptomatic progression (defined as worsening seizures or new or progressive neurologic deficits) or clinical progression (defined as initiation of treatment interventions such as radiotherapy, chemotherapy, or additional surgery).

OUTLINE:

Patients undergo neurocognitive assessment using the CogState Test battery (the Detection Test (DET), the Identification Test (IDN), the One Card Learning Test (OCLT), and the Groton Maze Learning Test (GMLT)) at baseline* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC Quality of Life Questionnaire-Core 30 (QOL-30), the Brain Cancer Module-20 (BCM20), and the European Quality of Life-5 Dimensions (EQ-5D) questionnaires at baseline*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study.

Patients undergo MRI scans at baseline*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.

NOTE: * 12 weeks after surgery.

Being tested
cognitive assessment, magnetic resonance imaging, laboratory biomarker analysis, questionnaire administration, quality-of-life assessment
Medical subject headings
Astrocytoma, Glioma, Oligodendroglioma, Neurotoxicity Syndromes, Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cognitive assessmentProcedure or surgery

    Undergo neurocognitive assessment

  • magnetic resonance imagingProcedure or surgery

    Also called MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging

    Undergo MRI

  • laboratory biomarker analysisOther

    Correlative studies

  • questionnaire administrationOther

    Ancillary studies

  • quality-of-life assessmentProcedure or surgery

    Also called quality of life assessment

    Ancillary studies

Study groups in NCT01417507
Study groupRoleWhat they receive
Supportive care (neurocognitive assessment and MRI)Patients undergo neurocognitive assessment using the CogState Test battery (the DET, the IDN, the OCLT, and the GMLT) at baseline* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC QOL-30, the BCM20, and the EQ-5D questionnaires at baseline*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study. Patients undergo MRI scans at baseline*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.
Receives: Procedure: cognitive assessment; Procedure: magnetic resonance imaging; Other: laboratory biomarker analysis; Other: questionnaire administration; Procedure: quality-of-life assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT)

    Each of the battery's tests will be evaluated using the 2-sample t-test with a 2-sided significance level of 0.05 to determine if there is a clinically meaningful difference in the average change of NCF score from baseline to the time of radiologic tumor progression or up to 5 years (whichever occurs first) between radiologically progressed and non-progressed patients. In order to adjust for multiple comparisons and maintain the overall type I error of 0.05, Hochberg's procedure will be applied.

    Measured: Up to 5 years

Secondary outcomes (9)

  1. Time to neurocognitive decline in patients who progress and who do not progress radiologically, as defined by the RCI-WSD

    The cumulative incidence approach will be used to estimate the median time to neurocognitive impairment to account for the competing risk of death and to determine if there is a clinically meaningful difference in the time to neurocognitive decline, as defined by the RCI-WSD (reliable change index-within-subjects standard deviation), between radiologically progressed and non-progressed patients.

    Measured: Up to 5 years

  2. PFS

    Estimated using the Kaplan-Meier method, and difference between the activation of different signaling pathways will be tested using the log rank test. Multivariate analyses with the Cox proportional hazards model for PFS will be performed to assess the activation of the signaling pathway effect adjusting for patient-specific risk factors. The covariates to be evaluated for the multivariate models are: activation of signaling pathway status, age, tumor size, and other prognostic factors.

    Measured: The interval from registration to progression or death, whichever occurs first, assessed up to 5 years

  3. Radiological progression

    To determine if the NCF decline is an earlier warning biomarker to radiologic progression, we will use NCF change as a time-dependent covariate in a Cox proportional hazards (PH) regression model with radiological progression as the endpoint. The Cox model estimates the ratio of hazard rate of radiographic failure with and without neurocognitive decline. Anticonvulsant use, tumor size, tumor histology, and further treatment received if recurrence is discovered, which may also have impact on the radiological progression, will also be considered in this Cox PH regression analysis.

    Measured: Up to 5 years

  4. Effect of salvage therapy on cognitive outcomes in patients who progress

    Measured: Up to 5 years

  5. QOL as measured by the EORTC QOL-30, EORTC QOL-BCN20, and EQ-5D

    The general linear mixed-effects model will be used to evaluate the changes of QOL and health utilities over time.

    Measured: Up to 5 years

  6. Frequency of seizures, evaluated using patient seizure diary

    Marginal models will be used to evaluate the change of frequencies of seizures over time for up to 5 years. Anticonvulsant use, tumor size, tumor histology, further treatment received if recurrence is discovered, and other prognostic factors will also be included in the covariates sets. The available molecular marker information will also be included as a covariate to evaluate the molecular correlates of seizure frequency.

    Measured: Up to 5 years

  7. Molecular correlates of QOL, NCF, seizure control, and PFS

    Measured: Up to 5 years

  8. OS

    Estimated using the Kaplan-Meier method, and difference between the activation of different signaling pathways will be tested using the log rank test. Multivariate analyses with the Cox proportional hazards model for OS will be performed to assess the activation of the signaling pathway effect adjusting for patient-specific risk factors. The covariates to be evaluated for the multivariate models are: activation of signaling pathway status, age, tumor size, and other prognostic factors.

    Measured: Up to 5 years

  9. Symptomatic or clinical progression

    Symptomatic and clinical progression will be explored for the correlation with cognitive changes in addition to radiological progression.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2011 (estimated)
  2. Study startOct 2011
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01417507
Sponsor's protocol ID
RTOG 0925
Other IDs
NCI-2011-02982, CDR0000708271, U10CA037422
Status last verified
Mar 2015
First submitted
13 Aug 2011
Last updated
18 Mar 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

An observational study of Adult Diffuse Astrocytoma and Adult Mixed Glioma, run by Radiation Therapy Oncology Group at 41 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01417507.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in