We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01227954
First Posted: October 25, 2010
Last Update Posted: September 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells.

PURPOSE: This phase II trial is studying how well avoiding the hippocampus during whole-brain radiation therapy works in treating patients with brain metastases.


Condition Intervention Phase
Cognitive/Functional Effects Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific Radiation: intensity-modulated radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases

Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Baseline and 4 months from start of treatment ]
    Change in Hopkins Verbal Learning Test-Revised delayed recall (HVLT_R DR) score from baseline to 4 months after the start of treatment calculated as (baseline score - 4 month score)/ baseline score. A positive change indicates a decline in function. The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms, helping to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. Delayed recall involves recalling a list of 12 targets after a 20-minute delay. The score is the sum of the number of targets correctly recalled. Percent change calculated as 100*[(baseline score - 4 month score)/ baseline score]


Secondary Outcome Measures:
  • Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT) [ Time Frame: Baseline and 4 months from start of treatment ]
    The score is the total number of correct responses made in remembering the list on three consecutive trials in a single session. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in ISLT score from baseline to 4 months was calculated as 100*[(baseline score - 4 month score)/ baseline score].

  • Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT) [ Time Frame: Baseline and 4 months from start of treatment ]
    The score is the arcsine of the square root of the proportion of correct responses. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in OCLT score from baseline to 4 months was calculated as 100*[(baseline score - 4 month score)/ baseline score].

  • Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) [ Time Frame: Baseline and 4 months from start of treatment ]
    The FACT-Br is a 19-item self-report instrument designed to measure multidimensional quality of life in patients with brain cancer. It is to be administered with the FACT-General. The FACT-G is a validated, 27-item measure where a higher score represents higher QOL. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, 0=Not a lot to 4=Very much. All subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range 0-108 for FACT-G total, 0-28 for physical, social, functional subscales, 0-24 for emotional subscale, 0-76 for brain subscale. Certain items must be reversed before it is added by subtracting the response from 4. Subscale requires >= 50% of items to be completed while the overall response rate must be > 80%. If items are missing, the subscale scores can be prorated.

  • Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) [ Time Frame: Baseline and 4 months from start of treatment ]
    The Barthel Index of Activities of Daily Living (ADL) is a 10-item assessment. Patient scores on the ADL range from 0 to 20 with lower scores indicating declining functional status.

  • Overall Survival [ Time Frame: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.) ]
    Overall survival was measured from registration to the date of death or last known follow-up (censored). Kaplan-Meier estimator was used to median survival time and 95% confidence interval.

  • Progression-free Survival [ Time Frame: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.) ]
    Progression (radiographic) is defined as an increase in perpendicular bidimensional tumor area (at lease 50% for lesions < 1cm, at least 25% for lesions >=1cm) for any of the 1-3 tracked brain metastases, or the appearance of any new brain metastasis on a follow-up MRI. Progression-free survival was calculated instead of time to progression. Progression-free survival time was measured from registration to the date of progression, death, or last known follow-up (censored). The Kaplan-Meier method used to determine median time (along with 95% confidence intervals).

  • The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to Treatment [ Time Frame: From start of treatment to 12 months from start of treatment ]
    For each patient the highest grade adverse event related to treatment was calculated. Those with their highest grade of 3 or higher were counted. Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE

  • ApoE4 Genotype and Other Potentially Predictive Biomarkers of Cognitive Function [ Time Frame: Baseline and 4 months from start of treatment ]
    Per the protocol, the feasibility of the proposed translational studies were to be assessed following completion of accrual and sample collection. The decision was made not to pursue this outcome measure. No assays were performed and no data were collected for this Outcome Measure


Enrollment: 113
Study Start Date: March 2011
Study Completion Date: December 2016
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
WBRT with Hippocampal Avoidance
Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Radiation: intensity-modulated radiation therapy
30 Gy in 10 fractions to the whole brain using intensity-modulated radiation therapy excluding the hippocampal avoidance area. Bilateral hippocampal contours manually generated on the fused planning MRI CT image set by the treating physician according to protocol-specified contouring instructions. Hippocampal avoidance regions generated by three-dimensionally expanding the hippocampal contours by 5 mm.
Other Name: IMRT

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate delayed recall as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R) at 4 months after hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) in patients with brain metastasis.

Secondary

  • Evaluate auditory and visual learning and memory, as assessed by two CogState tests (International Shopping List Test and One Card Learning Test), after HA-WBRT in these patients.
  • Compare psychometric properties of the 2 CogState tests to the HVLT-R for the assessment of memory decline after HA-WBRT in these patients.
  • Evaluate health-related quality of life [as assessed by the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR) and the Barthel Index of Activities of Daily Living (ADLs)] after HA-WBRT in these patients.
  • Evaluate time to radiographic progression after HA-WBRT in these patients.
  • Evaluate overall survival of these patients after HA-WBR.
  • Evaluate the adverse events of HA-WBR.
  • Evaluate predictive biomarkers of cognitive function.

OUTLINE: This is a multicenter study.

Patients undergo 10 fractions of intensity-modulated whole-brain radiotherapy (WBRT), avoiding hippocampal (HA) regions, once daily, 5 days a week, for 2-2½ weeks.

Patients neurocognitive functions (delayed recall, auditory and visual learning, and memory) are evaluated by the Hopkins Verbal Learning Test-Revised (HVTL-R), The One Card Learning Test (OCLT), and the International Shopping List Test (ISLT) at baseline and periodically during study.

Patients may undergo serum, plasma, or whole blood collection at baseline and at 4 months after completion of HA-WBRT for correlative studies.

Patients may complete the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR), and the Barthel Index of Activities of Daily Living (ADLs) quality-of-life questionnaires at baseline and periodically during study and follow up.

After completion of study therapy, patients are followed up periodically.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Histologically or cytologically confirmed non-hematopoietic malignancy within the past 5 years

    • If histologic proof of malignancy is from > 5 years ago, then a more recent pathological confirmation is required (e.g., from systemic metastatic or brain metastasis)
    • Patients with metastasis of unknown primary tumor are permitted
  • Measurable brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast-enhanced MRI obtained within the past 30 days
  • Have not been or will not be treated with stereotactic radiosurgery (SRS) or surgical resection

    • These treatment options are allowed only at relapse
  • Patients who have brain metastases at initial presentation allowed and do not need to demonstrate 3 months of stable scans
  • At least 1 week since open biopsy
  • Karnofsky performance status 70-100%
  • Fertile patients must use effective contraception
  • Negative pregnancy test 2 weeks or less prior to study entry
  • Patients must be English proficient, with patients who speak English as a second language eligible

EXCLUSION CRITERIA:

  • Small cell lung cancer or germ cell malignancy
  • Leptomeningeal metastases
  • Non-small cell lung cancer-associated brain metastases with ≥ 2 organ sites of extracranial metastases
  • Radiologic evidence of hydrocephalus
  • Serum creatinine > 1.4 mg/dL within 30 days prior to study entry
  • Pregnant or nursing
  • Contraindication to MRI imaging such as implanted metal devices or foreign bodies or severe claustrophobia
  • Severe, active co-morbidity including any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Uncontrolled, clinically significant cardiac arrhythmias
  • Prior radiotherapy to the brain
  • Plan for chemotherapy or targeted therapies during WBRT or during the subsequent 7 days
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01227954


  Show 63 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Minesh P. Mehta, MD University of Maryland Medical Systems
  More Information

Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01227954     History of Changes
Obsolete Identifiers: NCT01366755
Other Study ID Numbers: RTOG-0933
CDR0000687490
First Submitted: October 22, 2010
First Posted: October 25, 2010
Results First Submitted: August 23, 2017
Results First Posted: September 27, 2017
Last Update Posted: September 27, 2017
Last Verified: September 2017

Keywords provided by Radiation Therapy Oncology Group:
cognitive/functional effects
tumors metastatic to brain
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes