Neurocognitive Outcomes In Patients Treated With Radiotherapy For Five Or More Brain Metastases (NAGKC 12-01)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University of California, San Francisco
Sponsor:
Collaborator:
North American Gamma Knife Consortium
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01731704
First received: November 7, 2012
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

This is randomized study of neurocognitive outcomes in patients with five or more brain metastases treated with stereotactic radiosurgery (SRS), specifically the Gamma Knife (GK) system, or whole-brain radiation therapy (WBRT). The primary aim of this study is to compare the change in neurocognitive function outcome between baseline and 6 months in WBRT versus SRS treatment groups.


Condition Intervention
Brain Metastases
Radiation: Stereotactic radiosurgery (SRS)
Radiation: Whole brain radiation therapy (WBRT)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Controlled Study Of Neurocognitive Outcomes In Patients With Five Or More Brain Metastases Treated With Radiosurgery Or Whole-Brain Radiotherapy

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To compare the relative change in neurocognitive outcomes (change in oNCF z-score) between baseline and 6 months for surviving patients in upfront WBRT vs. SRS treatment groups. [ Time Frame: Every 3 months for 12 months ] [ Designated as safety issue: No ]

    All participants will be asked to complete:

    1. Online brain function testing: Complete a short 20-minute online brain function (cognitive) assessment every 2 weeks (twice per month, at least 10-14 days apart).
    2. Quality of Life Questionnaire: Complete a self-reported (if patient) and caregiver quality of life questionnaires every 10-12 weeks (2.5-3 months). These questionnaires take approximately 15-20 minutes to complete and can be done online or in clinic during follow-up visits.


Secondary Outcome Measures:
  • To compare the relative change in neurocognitive outcomes (change in oNCF z-score) between baseline and 12 months for surviving patients in upfront WBRT vs. SRS treatment groups. [ Time Frame: Every 10-12 weeks for 12 months after treatment ] [ Designated as safety issue: No ]
    • Neurocognitive function, 12-months post whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS)specifically the Gamma Knife (GK) system, treatment as measured by the online neurocognitive function (oNCF) composite z-score.
    • Neurocognitive function at all time points as measured by the online neurocognitive function (oNCF) composite z-score.

  • To compare the relative impact of initial therapy on patients' quality of life (QoL) as measured by caregiver assessments [ Time Frame: Every 10-12 weeks for 12 months after treatment ] [ Designated as safety issue: No ]
    • Quality of life (patient-reported measures) as measured by Beck Depression Inventory, Beck Anxiety Inventory, FACT-Br, FACT-Cog, Fatigue Severity Scale, EuroQol(EQ5D), EORTC-BN20, and QOL-30.

  • To compare the relative impact of initial therapy on patients' quality of life (QoL) as measured by caregiver assessments [ Time Frame: Every 10-12 months ] [ Designated as safety issue: No ]
    Quality of life as measured by caregiver assessments including Frontal Systems Behavior Scale, Neuropsychiatric Inventory, Functional Activities Questionnaire, and Everyday Cognition Questionnaire.

  • To estimate consistency and change in z-scores for oNCF assessments over all study endpoints in surviving patients treated with upfront whole brain radiation therapy (WBRT) vs. stereotactic radiosurgery (SRS). [ Time Frame: Every 10-12 months ] [ Designated as safety issue: No ]
  • To compare proportions of patients in the two treatment groups that require salvage therapy as a function of systemic disease control (controlled vs. uncontrolled). [ Time Frame: 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]
  • To compare the overall survival between patients in upfront whole brain radiation therapy (WBRT) vs. stereotactic radiosurgery (SRS) treatment groups [ Time Frame: baseline to study completion ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Cost analysis [ Time Frame: Prior to treatment up to 12 months after treatment is complete ] [ Designated as safety issue: Yes ]
    To determine what healthcare cost data can be collected in patients with metastatic disease within a context of a multi-institutional clinical trial.


Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Stereotactic Radiosurgery (SRS)
Radiation Therapy: Radiosurgical (SRS) technique via Gamma Knife Perfexion radiosurgical system
Radiation: Stereotactic radiosurgery (SRS)
Other Name: Gamma knife Perfexion radiosurgical device
Active Comparator: Whole Brain Radiation Therapy (WBRT)
whole-brain radiation therapy 30 Gy in 10 fractions. Treatment will be delivered once daily, 5 fractions per week, over 2 to 2.5 weeks
Radiation: Whole brain radiation therapy (WBRT)
External beam whole-brain radiation therapy 30 Gy in 10 fractions. Treatment will be delivered once daily, 5 fractions per week, over 2 to 2.5 weeks

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological confirmation is required (e.g. from extra- or intra-cranial disease).
  • If an open biopsy is performed, the patient must be at least one week post biopsy. This requirement does not apply to patients who undergo stereotactic biopsies.
  • Patients with ≥5 measurable brain metastases on a diagnostic-quality contrast-enhanced magnetic resonance imaging (MRI) obtained within 30 days prior to registration.
  • Patients with ≤10 cc largest tumor volume, and ≤15 cc total tumor volume.
  • History/physical examination within 30 days prior to registration.
  • Age ≥18 years.
  • Karnofsky performance status ≥70 (RTOG recursive partitioning analysis (RPA) Class I & II).
  • Minimum pre-treatment oNCF score ≥70.
  • Patients must provide study-specific informed consent prior to study entry.
  • Women of child-bearing age must have a negative, quantitative serum pregnancy test ≤14 days prior to study entry, or have a documented reason why such a test is not necessary (e.g. history of tubal ligation).
  • Patients must be able to speak and read English fluently (required for the use of online NCF testing).
  • Patients must demonstrate basic computer literacy skills and have access to an internet terminal (required for the use of online NCF testing).

Exclusion Criteria:

  • Clinical (e.g. multiple new cranial nerve deficits in the absence of obvious radiographic disease to explain symptoms) or radiographic evidence of leptomeningeal disease.
  • Patients with measurable brain metastasis(es) resulting from small cell lung cancer and/or germ cell malignancy.
  • No documentation of prior cytotoxic or other therapy for malignancy if such therapy was previously received. Note: This does not apply to patients with synchronous metastases at initial diagnosis.
  • Contraindication to MR imaging, such as implanted metal devices or foreign bodies, severe claustrophobia, or contraindications to contrast agent administration.
  • Estimated glomerular filtration rate (eGFR) <60 within 6 weeks prior to registration. • Prior radiation therapy to the brain. • Severe, active co-morbidity, defined as follows:

    • Unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months.
    • Transmural myocardial infarction within the last 6 months. - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
    • 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 at the time of registration.
    • Uncontrolled, clinically significant cardiac arrhythmias. - Radiologic or clinical evidence of hydrocephalus, or history of previously treated hydrocephalus.
  • Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study is potentially teratogenic
  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: NCT01731704

Contacts
Contact: Igor J Barani, MD 415-353-8900 baranii@radonc.ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Igor J Barani, MD    415-353-8900    baranii@radonc.ucsf.edu   
Principal Investigator: Igor J Barani, MD         
Sponsors and Collaborators
University of California, San Francisco
North American Gamma Knife Consortium
Investigators
Study Chair: Igor J Barani, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01731704     History of Changes
Other Study ID Numbers: 121010/12-01
Study First Received: November 7, 2012
Last Updated: September 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
5 or more brain metastases
proven diagnosis of a non-hematopoietic malignancy
non-small cell lung cancer or germ cell malignancy

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on August 20, 2014