- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02147028
Hippocampal Sparing Whole Brain Radiotherapy vs Conventional Whole Brain Radiotherapy in Patients With Brain Metastases (HIPPO)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Cambridge, United Kingdom
- Addenbrooke's Hospital
-
Guildford, United Kingdom
- Royal Surrey County Hospital
-
London, United Kingdom, W6 8RF
- Charing Cross Hospital
-
Manchester, United Kingdom, M20 4BX
- The Christie NHS Foundation Trust
-
Nottingham, United Kingdom
- Nottingham University Hospitals
-
Romford, United Kingdom
- Barking, Havering and Redbridge University Hospitals NHS Trust
-
-
Greater London
-
Birmingham, Greater London, United Kingdom, N4 3SL
- University Hospitals Birmingham NHS Foundation Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / 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
|
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
|
30 Gy in 10 fractions conventional whole brain radiotherapy will be administered
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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]
|
4 months after completion of WBRT or HS-WBRT
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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, 4, 6, 12 and 24 months after completion of WBRT or HS-WBRT
|
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
|
2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
|
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
|
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
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
|
2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
|
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
|
followed up until 24 months after completion of WBRT or HS-WBRT
|
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
|
2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
|
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
|
2, 4, 6, 9, 12, 18 and 24 months after completion of WBRT or HS-WBRT
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Gillian Whitfield, MA,MB BS,PhD, The Christie NHS Foundation Trust
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCL/12/0512
- Cancer Research UK (Other Grant/Funding Number: CRUK/11/010)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Brain Metastases
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingRecurrent Brain Metastases | Progressive Brain MetastasesUnited States
-
AC Camargo Cancer CenterCarl Zeiss Meditec AGTerminatedBrain Metastases, Adult | Central Nervous System MetastasesBrazil
-
Rigshospitalet, DenmarkRecruitingCancer | Brain Metastases, AdultDenmark
-
Susanne RogersUniversity of Basel; Technical University of MunichRecruitingBrain Metastases, AdultSwitzerland
-
British Columbia Cancer AgencyVarian Medical SystemsRecruitingBrain Metastases, AdultCanada
-
IRCCS San RaffaeleRecruitingBrain Metastases, AdultItaly
-
AHS Cancer Control AlbertaRecruitingBrain Metastases, AdultCanada
-
University Health Network, TorontoRecruiting
-
Centre Francois BaclesseGroupement Interrégional de Recherche Clinique et d'Innovation; ANOCEF/IGCNORecruitingHemorrhagic Brain MetastasesFrance
-
Duke UniversityVarian Medical SystemsCompleted
Clinical Trials on Hippocampal sparing whole brain radiotherapy
-
Kaohsiung Medical University Chung-Ho Memorial...UnknownBrain Metastases | Neurocognitive FunctionTaiwan
-
Ottawa Hospital Research InstituteNot yet recruitingBrain Metastases | Radiosurgery
-
University Hospital, EssenUnknown
-
Mediterranean Institute of OncologyUniversity of Palermo; University of MessinaRecruitingQuality of Life | Neurocognitive Deficit | Activities of Daily LivingItaly
-
Affiliated Hospital to Academy of Military Medical...UnknownBrain Metastases | Breast Cancer MetastaticChina
-
Chang Gung Memorial HospitalRecruiting
-
Chang Gung Memorial HospitalRecruitingBrain Metastasis | Brain MetastasesTaiwan
-
Chang Gung Memorial HospitalRecruitingBrain Metastasis | Non-Small-Cell Lung Cancer (NSCLC)Taiwan
-
Institut de Cancérologie de LorraineCompleted
-
Xiaorong DongNot yet recruitingCarcinoma, Non-Small-Cell Lung | Brain MetastasesChina