Neurocognitive Outcomes In Patients Treated With Radiotherapy For Five Or More Brain Metastases

NCT01731704 | Withdrawn DMC

• 1 other identifier: 121010/12-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Metastases

Keywords

5 or more brain metastases; proven diagnosis of a non-hematopoietic malignancy; non-small cell lung cancer or germ cell malignancy

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Every 3 months for 12 months

Secondary Outcomes (6)

• 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.

  Every 10-12 weeks for 12 months after treatment

• To compare the relative impact of initial therapy on patients' quality of life (QoL) as measured by caregiver assessments

  Every 10-12 weeks for 12 months after treatment

• To compare the relative impact of initial therapy on patients' quality of life (QoL) as measured by caregiver assessments

  Every 10-12 months

• 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).

  Every 10-12 months

• To compare proportions of patients in the two treatment groups that require salvage therapy as a function of systemic disease control (controlled vs. uncontrolled).

  3, 6, 9, and 12 months

Other Outcomes (1)

• Cost analysis

  Prior to treatment up to 12 months after treatment is complete

Study Arms (2)

Stereotactic Radiosurgery (SRS)

ACTIVE COMPARATOR

Radiation Therapy: Radiosurgical (SRS) technique via Gamma Knife Perfexion radiosurgical system

Radiation: Stereotactic radiosurgery (SRS)

Whole Brain Radiation Therapy (WBRT)

ACTIVE COMPARATOR

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)

Interventions

Stereotactic radiosurgery (SRS) RADIATION

Also known as: Gamma knife Perfexion radiosurgical device

Stereotactic Radiosurgery (SRS)

Whole brain radiation therapy (WBRT) RADIATION

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

Whole Brain Radiation Therapy (WBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• North American Gamma Knife Consortium: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Igor J Barani, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2012
• First Posted: November 22, 2012
• Study Start: December 1, 2012
• Primary Completion: October 26, 2015
• Study Completion: December 1, 2018
• Last Updated: March 14, 2017

Record last verified: 2017-03

Locations

US (1)