Clinical trial NCT02147028: Hippocampal Sparing Whole Brain Radiotherapy vs Conventional Whole Brain Radiotherapy in Patients With Brain Metastases
Official title: A Randomized Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Metastases
Keywords: whole brain RT
hippocampal sparing
neurocognitive function
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: The Brain Tumour Charity
First posted: 2014-05-26
Enrollment: 23
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether sparing the hippocampi during whole brain radiotherapy following neurosurgery or stereotactic radiosurgery in patients with brain metastases from a systemic tumour helps preserve brain function.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 16 years
* Karnofsky Performance Status (KPS) ≥ 70
* Brain metastases from systemic malignancy which has been histologically confirmed (from the primary or any metastatic site)
* In total, at most 10 distinct brain metastases based on MRI imaging with contrast at any prior time-points
* Each of the brain metastases to have been treated by complete or incomplete surgical excision or by SRS in line with UK SRS commissioning guidelines which in addition for STS treated patients means:

  * Patient selection for SRS by the appropriate MDT(s),
  * No pressure symptoms which would be best relieved by surgery,
  * Life expectancy from extracranial disease greater than 6 months,
  * Gross tumour volume at time of SRS ≤ 20 cc.
* Ability to comply with the following timelines:

  * Randomisation 1 - 4 weeks (+/- 3 days, but only acceptable if accounting for logistical issues) after neurosurgery or last SRS fraction,
  * Start of WBRT or HS-WBRT 4 - 6 weeks (+ 3 days, but only acceptable if accounting for logistical or planning treatment issues) after neurosurgery or last SRS fraction.
* Ability to complete the NCF test battery (including ability to speak English).
* Willing and able to give consent and to comply with treatment and follow up schedule.

Exclusion Criteria:

* Metastases from small cell carcinoma from any site, haematological malignancy, or central nervous system malignancy,
* Leptomeningeal metastases,
* Contraindication to MRI imaging with contrast,
* Prior radiotherapy to the brain (apart from a single course of SRS for brain metastases completed within 1-4 weeks (+/- 3 days) of randomisation and within 4-6 weeks (+3 days) of start of the HIPPO trial treatment),
* Prior neurosurgery for brain metastases (apart from a single operation within 1-4 weeks (+/- 3 days) of randomisation and within 4-6 weeks (+3 days) of start of HIPPO trial treatment), except that one or more earlier operations not immediately preceding HIPPO trial entry will be allowed if:

  * there is no evidence of residual tumour at the resection site on contrast MRI imaging, or
  * residual tumour at the resection site has been treated by SRS immediately prior to entering the HIPPO trial,
* One or more metastases currently or previously within 5 mm of either hippocampus,
* One or more metastases within the brainstem,
* One or more SRS treated metastases in close proximity to critical normal organs, unless the local investigator is satisfied that the dose already received by the critical organ allows for subsequent delivery of the HIPPO protocol radiotherapy doses,
* Disease specific graded prognostic assessment (DS-GPA) score ≤ 1.0 for any of the histologies for which DS-GPA has been defined,
* Past medical history of dementia which is thought to be unrelated to the brain metastases,
* Women of childbearing potential who are known to be pregnant, or are unwilling to use an acceptable method of contraception from the time of informed consent until completion of the course of radiotherapy.

Primary outcomes:
measure: Total recall assessed using Hopkins Verbal Learning Test-Revised (HVTLR) at 4 months
timeFrame: 4 months after completion of WBRT or HS-WBRT
Secondary outcomes:
measure: Neurocognitive function
timeFrame: 2, 4, 6, 12 and 24 months after completion of WBRT or HS-WBRT
measure: Quality of life
timeFrame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
measure: Length of time functionally independent
timeFrame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
measure: Local control of surgery/SRS treated metastases, local and distant intracranial control (treated and new metastases), and disease control within the hippocampal regions
timeFrame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
measure: Overall survival
timeFrame: followed up until 24 months after completion of WBRT or HS-WBRT
measure: Steroid and antiepileptic medication requirements
timeFrame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
measure: Acute and late side effects of radiotherapy
timeFrame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: Greater London
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge University Hospitals Nhs Trust
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Gillian Whitfield, MA,MB BS,PhD
role: STUDY_CHAIR
References: