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Hippocampal Sparing Whole Brain Radiotherapy vs Conventional Whole Brain Radiotherapy in Patients With Brain Metastases (HIPPO)

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ClinicalTrials.gov Identifier: NCT02147028
Recruitment Status : Active, not recruiting
First Posted : May 26, 2014
Last Update Posted : October 11, 2018
Sponsor:
Collaborators:
Cancer Research UK
The Brain Tumour Charity
Information provided by (Responsible Party):
University College, London

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.

Condition or disease Intervention/treatment Phase
Brain Metastases Radiation: Hippocampal sparing whole brain radiotherapy Radiation: Conventional whole brain radiotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2016
Actual Primary Completion Date : June 2018
Estimated Study Completion Date : January 2020

Arm Intervention/treatment
Experimental: Hippocampal sparing whole brain RT
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
30 Gy in 10 fractions hippocampal sparing whole brain radiotherapy will be administered by Helical Tomotherapy, IMRT, or VMAT

Active Comparator: Control: Conventional whole brain RT
30 Gy in 10 fractions conventional whole brain radiotherapy will be administered
Radiation: Conventional whole brain radiotherapy
30 Gy in 10 fractions conventional whole brain radiotherapy will be administered




Primary Outcome Measures :
  1. Total recall assessed using Hopkins Verbal Learning Test-Revised (HVTLR) at 4 months [ Time Frame: 4 months after completion of WBRT or HS-WBRT ]
    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]


Secondary Outcome Measures :
  1. Neurocognitive function [ Time Frame: 2, 4, 6, 12 and 24 months after completion of WBRT or HS-WBRT ]
    NCF, using a 30-60 min test battery (Memory - HVLT-R, Wechsler Memory Scale (logical memory subtest), Rey figure test, Wechsler digit span; Attention - Test of Everyday Attention (map search subtest), Trail Making Test (Parts A and B); Language - Graded Naming Test); this may be revised in the light of forthcoming recommendations on NCF assessment in brain metastases trials by the RANO (Revised Assessment in Neuro-oncology) working party

  2. Quality of life [ Time Frame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT ]
    Quality of life will be assessed using EORTC QLQ C30 and BN20 and EuroQol EQ-5D questionnaires

  3. Length of time functionally independent [ Time Frame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT ]
    The duration of functional independence will be assessed as the time for which the Karnofsky Performance Status ≥ 70

  4. Local control of surgery/SRS treated metastases, local and distant intracranial control (treated and new metastases), and disease control within the hippocampal regions [ Time Frame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT ]
    Incidence of metastases within the perihippocampal region, local control, and intracranial control will be assessed on the basis of MRI imaging

  5. Overall survival [ Time Frame: followed up until 24 months after completion of WBRT or HS-WBRT ]
    Date of death will be determined from the medical records, or from the GP

  6. Steroid and antiepileptic medication requirements [ Time Frame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT ]
    Steroid and antiepileptic medication use will be recorded in patient diaries and assessed at clinic visits

  7. Acute and late side effects of radiotherapy [ Time Frame: 2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT ]
    Acute and late side effects of radiotherapy will be assessed using NCI CTCAE scale v4.03



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or incomplete surgical excision or by SRS in line with UK SRS comissioning 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02147028


Locations
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United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, Greater London, United Kingdom, N4 3SL
Addenbrooke's Hospital
Cambridge, United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
Charing Cross Hospital
London, United Kingdom, W6 8RF
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Nottingham University Hospitals
Nottingham, United Kingdom
Barking, Havering and Redbridge University Hospitals Nhs Trust
Romford, United Kingdom
Sponsors and Collaborators
University College, London
Cancer Research UK
The Brain Tumour Charity
Investigators
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Study Chair: Gillian Whitfield, MA,MB BS,PhD The Christie NHS Foundation Trust

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02147028     History of Changes
Other Study ID Numbers: UCL/12/0512
Cancer Research UK ( Other Grant/Funding Number: CRUK/13/017 )
First Posted: May 26, 2014    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Keywords provided by University College, London:
whole brain RT
hippocampal sparing
neurocognitive function
Additional relevant MeSH terms:
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Neoplasm Metastasis
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