Hippocampal Sparing Whole Brain Radiotherapy vs Conventional Whole Brain Radiotherapy in Patients With Brain Metastases

NCT02147028 | Completed Phase 2

• 2 other identifiers: UCL/12/0512Cancer Research UK
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 7

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.

Conditions

Brain Metastases

Keywords

whole brain RT; hippocampal sparing; neurocognitive function

Outcome Measures

Primary Outcomes (1)

• Total recall assessed using Hopkins Verbal Learning Test-Revised (HVTLR) at 4 months

  A decline in total recall will be assessed as being clinically significant if there is at least a 5 point decrease in total recall score at 4 months, compared to baseline \[Jacobson 1991, Brandt 1998\]

  4 months after completion of WBRT or HS-WBRT

Secondary Outcomes (7)

• Neurocognitive function

  2, 4, 6, 12 and 24 months after completion of WBRT or HS-WBRT

• Quality of life

  2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT

• Length of time functionally independent

  2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT

• Local control of surgery/SRS treated metastases, local and distant intracranial control (treated and new metastases), and disease control within the hippocampal regions

  2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT

• Overall survival

  followed up until 24 months after completion of WBRT or HS-WBRT

Study Arms (2)

Hippocampal sparing whole brain RT

EXPERIMENTAL

30 Gy in 10 fractions hippocampal sparing whole brain radiotherapy will be administered by Helical Tomotherapy, IMRT, or VMAT

Radiation: Hippocampal sparing whole brain radiotherapy

Control: Conventional whole brain RT

ACTIVE COMPARATOR

30 Gy in 10 fractions conventional whole brain radiotherapy will be administered

Radiation: Conventional whole brain radiotherapy

Interventions

Hippocampal sparing whole brain radiotherapy RADIATION

30 Gy in 10 fractions hippocampal sparing whole brain radiotherapy will be administered by Helical Tomotherapy, IMRT, or VMAT

Hippocampal sparing whole brain RT

Conventional whole brain radiotherapy RADIATION

30 Gy in 10 fractions conventional whole brain radiotherapy will be administered

Control: Conventional whole brain RT

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• The Brain Tumour Charity: collaborator

Study Sites (7)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, Greater London, N4 3SL, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Royal Surrey County Hospital

Guildford, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Barking, Havering and Redbridge University Hospitals Nhs Trust

Romford, United Kingdom

Location

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

• Gillian Whitfield, MA,MB BS,PhD

  The Christie NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: May 26, 2014
• Study Start: August 3, 2016
• Primary Completion: June 1, 2018
• Study Completion: February 16, 2021
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

GB (7)