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Cognitive/Functional EffectsPhase 2NCT01227954

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

A Phase 2 study testing intensity-modulated radiation therapy in people with Cognitive/Functional Effects and Metastatic Cancer, run by Radiation Therapy Oncology Group at 63 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
intensity-modulated radiation therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
113 participants
Where
63 sitesin 2 countries
Study dates
Mar 2011to Dec 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

63 sites in 2 countries.

63 sites in 2 countries

United States60 sites

  • Rosenfeld Cancer Center at Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Summa Center for Cancer Care at Akron City Hospital

    Akron, Ohio, 44309-2090

  • New York Oncology Hematology, PC at Albany Regional Cancer Care

    Albany, New York, 12206

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Texas Oncology, PA at Harris Center HEB

    Bedford, Texas, 76022

  • Billings Clinic - Downtown

    Billings, Montana, 59107-7000

  • UAB Comprehensive Cancer Center

    Birmingham, Alabama, 35294

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

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

    Chapel Hill, North Carolina, 27599-7295

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

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

    Columbus, Ohio, 43210-1240

  • NSMC Cancer Center - Peabody

    Danvers, Massachusetts, 01923

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Regional Cancer Center - Erie

    Erie, Pennsylvania, 16505

  • Willamette Valley Cancer Center - Eugene

    Eugene, Oregon, 97401

  • Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital

    Fort Worth, Texas, 76104

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • Center for Cancer Care at Goshen General Hospital

    Goshen, Indiana, 46526

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

    Hershey, Pennsylvania, 17033-0850

  • Memorial Hermann Hospital - Memorial City

    Houston, Texas, 77024

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • Methodist Cancer Center at Methodist Hospital

    Indianapolis, Indiana, 46202

  • Baptist Cancer Institute - Jacksonville

    Jacksonville, Florida, 32207

  • St. Barnabas Medical Center Cancer Center

    Livingston, New Jersey, 07039

  • Veterans Affairs Medical Center - Long Beach

    Long Beach, California, 90822

  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Baptist-South Miami Regional Cancer Program

    Miami, Florida, 33176

  • Southwest General Health Center

    Middleburg Heights, Ohio, 44130

  • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

    Murray, Utah, 84157

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

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

    Ogden, Utah, 84403

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Florida Cancer Center - Palatka

    Palatka, Florida, 32177

  • Arizona Center for Cancer Care - Peoria

    Peoria, Arizona, 85381

  • OSF St. Francis Medical Center

    Peoria, Illinois, 61637

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Providence Cancer Center at Providence Portland Medical Center

    Portland, Oregon, 97213-2967

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Radiological Associates of Sacramento Medical Group, Incorporated

    Sacramento, California, 95815

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • Huntsman Cancer Institute at University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

  • CCOP - Virginia Mason Research Center

    Seattle, Washington, 98101

  • Cancer Care Northwest - Spokane South

    Spokane, Washington, 99202

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land

    Sugar Land, Texas, 77479

  • Arizona Oncology - Tucson

    Tucson, Arizona, 85704

  • Arizona Cancer Center at University of Arizona Health Sciences Center

    Tucson, Arizona, 85724-5024

  • Lankenau Cancer Center at Lankenau Hospital

    Wynnewood, Pennsylvania, 19096

  • York Cancer Center at Apple Hill Medical Center

    York, Pennsylvania, 17405

Other trials in United States

Canada3 sites

  • London Regional Cancer Program at London Health Sciences Centre

    London, Ontario, N6A 4L6

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
intensity-modulated radiation therapy
Keywords
cognitive/functional effects, tumors metastatic to brain, unspecified adult solid tumor, protocol specific
Medical subject headings
Neoplasm Metastasis, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • intensity-modulated radiation therapyRadiation

    Also called IMRT

    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.

Study groups in NCT01227954
Study groupRoleWhat they receive
WBRT with Hippocampal AvoidanceOtherWhole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Receives: Radiation: intensity-modulated radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)

    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]

    Measured: Baseline and 4 months from start of treatment

Secondary outcomes (8)

  1. Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT)

    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].

    Measured: Baseline and 4 months from start of treatment

  2. Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT)

    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].

    Measured: Baseline and 4 months from start of treatment

  3. Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)

    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.

    Measured: Baseline and 4 months from start of treatment

  4. Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL)

    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.

    Measured: Baseline and 4 months from start of treatment

  5. Overall Survival

    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.

    Measured: 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.)

  6. Progression-free Survival

    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).

    Measured: 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.)

  7. The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to 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

    Measured: From start of treatment to 12 months from start of treatment

  8. ApoE4 Genotype and Other Potentially Predictive Biomarkers of Cognitive Function

    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

    Measured: Baseline and 4 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2010 (estimated)
  2. Study startMar 2011
  3. Primary completionMay 2013
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
113 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01227954
Sponsor's protocol ID
RTOG-0933
Other IDs
CDR0000687490
Status last verified
Sep 2017
First submitted
22 Oct 2010
Last updated
27 Sep 2017
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25349290

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing intensity-modulated radiation therapy in people with Cognitive/Functional Effects and Metastatic Cancer, run by Radiation Therapy Oncology Group at 63 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01227954, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.

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