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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01227954
First received: October 22, 2010
Last updated: January 7, 2014
Last verified: January 2014

October 22, 2010
January 7, 2014
March 2011
June 2016   (final data collection date for primary outcome measure)
Delayed recall at 4 months as measured by the Hopkins Verbal Learning Test-Revised [ Time Frame: Within 2 weeks prior to treatment, 4 months after HA-WBRT ] [ Designated as safety issue: No ]
Delayed recall at 4 months as measured by the Hopkins Verbal Learning Test-Revised [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01227954 on ClinicalTrials.gov Archive Site
  • Auditory and visual learning and memory as measured by the International Shopping List Test and One Card Learning Test (CogState) [ Time Frame: Within 2 weeks prior to treatment, 4 months after HA-WBRT ] [ Designated as safety issue: No ]
  • Quality of life as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Barthel Index of Activities of Daily Living (ADL) [ Time Frame: Within 2 weeks prior to treatment, 4 months after HA-WBRT ] [ Designated as safety issue: No ]
  • Time to radiographic progression [ Time Frame: Baseline to date of radiographic progression ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Baseline to date of death from any cause; patients last known to be alive are censored at date of last contact ] [ Designated as safety issue: No ]
  • Adverse events based on NCI CTCAE criteria [ Time Frame: Within 2 weeks prior to treatment, 2, 4 and 12 months after HA-WBRT ] [ Designated as safety issue: Yes ]
  • ApoE4 genotype and other potentially predictive biomarkers of cognitive function [ Time Frame: Within 2 weeks prior to treatment, 4 months ] [ Designated as safety issue: No ]
  • Auditory and visual learning and memory as measured by the International Shopping List Test and One Card Learning Test (CogState) [ Designated as safety issue: No ]
  • Quality of life as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Barthel Index of Activities of Daily Living (ADL) [ Designated as safety issue: No ]
  • Time to radiographic progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Adverse events based on NCI CTCAE criteria [ Designated as safety issue: Yes ]
  • ApoE4 genotype and other potentially predictive biomarkers of cognitive function [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases

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.

OBJECTIVES:

Primary

  • Evaluate delayed recall as assessed by the Hopkins Verbal Learning Test-Revised (HVTL-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 2 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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cognitive/Functional Effects
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Other: laboratory biomarker analysis
  • Other: questionnaire administration
  • Procedure: cognitive assessment
  • Procedure: quality-of-life assessment
  • Radiation: intensity-modulated radiation therapy
  • Radiation: whole-brain radiation therapy
HA-WBRT
Whole Brain Radiotherapy with Hippocampal avoidance using IMRT (30 Gy in 10 fractions)
Interventions:
  • Other: laboratory biomarker analysis
  • Other: questionnaire administration
  • Procedure: cognitive assessment
  • Procedure: quality-of-life assessment
  • Radiation: intensity-modulated radiation therapy
  • Radiation: whole-brain radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
113
Not Provided
June 2016   (final data collection date for primary outcome measure)

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 MR 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01227954
RTOG-0933, CDR0000687490
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Minesh P. Mehta, MD University of Maryland Medical Systems
Radiation Therapy Oncology Group
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP