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

NCT ID: NCT01227954

Last Updated: 2017-09-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

113 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cognitive/Functional Effects Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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WBRT with Hippocampal Avoidance

Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)

Group Type OTHER

intensity-modulated radiation therapy

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type RADIATION

Other Intervention Names

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IMRT

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Minesh P. Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland Medical Systems

Locations

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UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Arizona Center for Cancer Care - Peoria

Peoria, Arizona, United States

Site Status

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Arizona Oncology - Tucson

Tucson, Arizona, United States

Site Status

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

Veterans Affairs Medical Center - Long Beach

Long Beach, California, United States

Site Status

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Site Status

Florida Cancer Center - Palatka

Palatka, Florida, United States

Site Status

Piedmont Hospital

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

OSF St. Francis Medical Center

Peoria, Illinois, United States

Site Status

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

NSMC Cancer Center - Peabody

Danvers, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Billings Clinic - Downtown

Billings, Montana, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

St. Barnabas Medical Center Cancer Center

Livingston, New Jersey, United States

Site Status

New York Oncology Hematology, PC at Albany Regional Cancer Care

Albany, New York, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Site Status

Adena Regional Medical Center

Chillicothe, Ohio, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Southwest General Health Center

Middleburg Heights, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Willamette Valley Cancer Center - Eugene

Eugene, Oregon, United States

Site Status

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Rosenfeld Cancer Center at Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

Regional Cancer Center - Erie

Erie, Pennsylvania, United States

Site Status

Adams Cancer Center

Gettysburg, Pennsylvania, United States

Site Status

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

Site Status

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Texas Oncology, PA at Harris Center HEB

Bedford, Texas, United States

Site Status

Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital

Fort Worth, Texas, United States

Site Status

Memorial Hermann Hospital - Memorial City

Houston, Texas, United States

Site Status

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land

Sugar Land, Texas, United States

Site Status

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Site Status

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

Ogden, Utah, United States

Site Status

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Site Status

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27.

Reference Type RESULT
PMID: 25349290 (View on PubMed)

Other Identifiers

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CDR0000687490

Identifier Type: -

Identifier Source: secondary_id

RTOG-0933

Identifier Type: -

Identifier Source: org_study_id

NCT01366755

Identifier Type: -

Identifier Source: nct_alias