Neurocognitive Outcome of Conformal WBRT w/wo Hippocampal Avoidance for Brain Metastases

NCT02393131 | Unknown DMC

• 1 other identifier: 201412029RINB
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Brain metastases are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness. Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. WBRT yields high radiologic response rate (27\~56%) and is effective in rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function decline caused by intracranial lesions. By using conventional fractionation, 33% of patients developed late neurocognitive toxicity while memory impairment was the most common symptom. The incidence is even higher when a formal and sensitive neurocognitive assessment was prospectively evaluated. With more long-term survivors nowadays, it has become increasingly important to minimize neurocognitive function decline and maintain quality of life in patients with brain metastasis. The function of hippocampus is cooperation in learning, consolidation and retrieval of information and essential for formation of new memories. Bilateral and unilateral radiation injury of the hippocampus is known to alter learning and memory formation. Several preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is associated with subsequent neurocognitive function impairment in adult and pediatric patients. Furthermore, the preliminary result of Radiation Therapy Oncology Group (RTOG) 0933 suggested hippocampal avoidance significant reduce the mean relative decline at 4 months from 30% in historical cohort with WBRT to 7% in experimental cohort. Previous studies showed brain structures other than hippocampus are also associated with radiation-induced decline in neurocognitive function. There is presence of placebo effect for interventions seeking improvement in neurocognitive function. In present study, a single blind randomized phase II trial is designed to investigate the effectiveness of neurocognitive function preservation using conformal WBRT with or without hippocampal avoidance.

Conditions

Metastatic Malignant Neoplasm to Brain

Keywords

Brain Metastases; Whole Brain Radiotherapy; Neurocognitive function

Outcome Measures

Primary Outcomes (1)

• Hopkins Verbal Learning Test-Revised (HVTL-R) delayed recall score

  Decline in Hopkins Verbal Learning Test-Revised (HVTL-R) delayed recall score from baseline to 4 months after the start of conformal whole brain radiotherapy with or without hippocampal avoidance for brain metastases

  At 4 months after radiotherapy

Secondary Outcomes (6)

• Neurocognitive function by a standardized neurocognitive battery

  at 1, 2, 4, 6, 9, 12 months after radiotherapy, and then every 3 months until date of death from any cause, assessed up to 24 months

• Patient reported outcome (Quality of Life questionnaire)

  at 1, 2, 4, 6, 9, 12 months after radiotherapy, and then every 3 months until date of death from any cause, assessed up to 24 months

• Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)

  From date of radiotherapy until 90 days after radiotherapy starts

• Late toxicity (Common Toxicity Criteria for Adverse Events version 4)

  From 90 days after radiotherapy starts until the date of death from any cause, up to 60 months

• Intracranial progression (Number of participant with intracranial progression on MRI of brain)

  From date of enrolment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 60 months

Other Outcomes (1)

• Genomic risk of neurocognitive decline after WBRT

  At 4 months after radiotherapy

Study Arms (2)

Hippocampal avoidance WBRT

EXPERIMENTAL

Conformal whole brain radiotherapy with hippocampal avoidance

Radiation: Hippocampal avoidance WBRT

Conformal WBRT

ACTIVE COMPARATOR

Conformal whole brain radiotherapy without hippocampal avoidance

Radiation: Conformal WBRT

Interventions

Hippocampal avoidance WBRT RADIATION

Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy

Hippocampal avoidance WBRT

Conformal WBRT RADIATION

Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy

Conformal WBRT

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of brain metastases
• Patients with brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast enhanced MRI obtained within 30 days prior to registration
• Patients with brain metastasis who have not been or will not be treated with stereotactic radiosurgery (SRS) or have received SRS for≤ 5 intracranial metastatic lesions
• No evidence of leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration
• Age ≥ 20 years
• Karnofsky Performance Status ≥ 60%
• Life expectancy of ≥ 4 months.
• Women of childbearing potential and male participants must practice adequate contraception
• Patients must be able to comply with the study protocol and follow-up schedules and provide study- specific informed consent

You may not qualify if:

• Patients fulfill any of the following criteria will be excluded from this trial
• Prior radiotherapy to brain or SRS to \> 5 intracranial metastatic lesion(s) or the biological equivalent dose in 2-Gy fractions was greater than 7.3 Gy to 40% of the volume of bilateral hippocampus from prior SRS
• Serum creatinine \> 2.0 mg/dL within 30 days prior registration
• Contraindication to MRI such as implanted metal devices or foreign bodies, severe claustrophobia
• Patients with leptomeningeal metastases
• Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
• Uncontrolled active infection requiring intravenous antibiotics at the time of registration
• Transmural myocardial infarction ≤ 6 months prior to registration
• Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
• Life-threatening uncontrolled clinically significant cardiac arrhythmias
• 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 psychiatric disorder
• Uncontrolled, clinically significant cardiac arrhythmias
• Will receive any other investigational agent or chemotherapy and/or target therapies during WBRT

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

• Yang WC, Chen YF, Yang CC, Wu PF, Chan HM, Chen JL, Chen GY, Cheng JC, Kuo SH, Hsu FM. Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial. Neuro Oncol. 2021 Mar 25;23(3):478-486. doi: 10.1093/neuonc/noaa193.

  PMID: 32789503 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Feng-Ming Hsu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: March 19, 2015
• Study Start: March 3, 2015
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2020
• Last Updated: July 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)