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
  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
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
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 113
Study Start Date: March 2011
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
HA-WBRT
Whole Brain Radiotherapy with Hippocampal avoidance using IMRT (30 Gy in 10 fractions)
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227954

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

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01227954     History of Changes
Obsolete Identifiers: NCT01366755
Other Study ID Numbers: RTOG-0933, CDR0000687490
Study First Received: October 22, 2010
Last Updated: January 7, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

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
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014