Clinical trial NCT01227954: Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
Official title: A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cognitive/Functional Effects
Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: cognitive/functional effects
tumors metastatic to brain
unspecified adult solid tumor, protocol specific
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2010-10-25
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 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

Primary outcomes:
measure: Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)
timeFrame: Baseline and 4 months from start of treatment
Secondary outcomes:
measure: Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT)
timeFrame: Baseline and 4 months from start of treatment
measure: Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT)
timeFrame: Baseline and 4 months from start of treatment
measure: Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
timeFrame: Baseline and 4 months from start of treatment
measure: Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL)
timeFrame: Baseline and 4 months from start of treatment
measure: Overall Survival
timeFrame: 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.)
measure: Progression-free Survival
timeFrame: 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.)
measure: The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to Treatment
timeFrame: From start of treatment to 12 months from start of treatment
measure: ApoE4 Genotype and Other Potentially Predictive Biomarkers of Cognitive Function
timeFrame: Baseline and 4 months from start of treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Peoria
country: United States
facility: Arizona Center for Cancer Care - Peoria
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology - Tucson
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
city: Long Beach
country: United States
facility: Veterans Affairs Medical Center - Long Beach
state: California
city: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Palatka
country: United States
facility: Florida Cancer Center - Palatka
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Danvers
country: United States
facility: NSMC Cancer Center - Peabody
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Livingston
country: United States
facility: St. Barnabas Medical Center Cancer Center
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, PC at Albany Regional Cancer Care
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Southwest General Health Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Center - Eugene
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Erie
country: United States
facility: Regional Cancer Center - Erie
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Bedford
country: United States
facility: Texas Oncology, PA at Harris Center HEB
state: Texas
city: Fort Worth
country: United States
facility: Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital - Memorial City
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land
state: Texas
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Maryland Medical Systems
name: Minesh P. Mehta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.