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Trial registered on ANZCTR


Registration number
ACTRN12617000138381
Ethics application status
Approved
Date submitted
18/01/2017
Date registered
25/01/2017
Date last updated
21/01/2019
Date data sharing statement initially provided
21/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study of Hippocampal Avoidance Technique for Whole Brain Radiotherapy in stage IV breast cancer with brain metastases
Scientific title
Pilot study to evaluate the effect of Hippocampal Avoidance Technique for Whole Brain Radiotherapy on neurocognitive function in patients with stage IV breast cancer with brain metastases
Secondary ID [1] 290962 0
none
Universal Trial Number (UTN)
U1111-1191-7852
Trial acronym
HATS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 301703 0
Brain Metastases 301704 0
Condition category
Condition code
Cancer 301403 301403 0 0
Breast
Cancer 301415 301415 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be treated with volumetric modulated arc therapy at Perth Radiation Oncology Centre, WA. All treatment will be planned by Radiation Oncologists and treatment delivered by trained Radiation Therapists. Simulation and treatment will occur with the patient immobilised in a supine position using a head cast and custom headrest. The chin will be tucked to ensure the optical apparatus are not in the same plane as the hippocampus and reduce the impact of dental artefacts. For the purpose of treatment planning a non-contrast head CT with an axial slice thickness of 1 mm will be acquired. This will be fused with a contrast enhanced brain MRI scan to be done within 14 days of expected commencement of radiotherapy. If a baseline brain MRI has been done that is acceptable for planning purposes within 28 days of expected radiotherapy commencement then this may be utilised at the discretion of the treating radiation oncologist.
. Prescribed dose will be 30 Gy in 10 fractions, to be delivered over 2 weeks, at 5 fractions per week and 3 Gy per fraction. Extension of treatment duration by up to 3 standard treatment days will be considered an acceptable deviation if unavoidable due to clinical or technical limitations that arise. Hippocampal dose limits will be D100% < 9 Gy and Dmax < 16 Gy. Deviations of D100% < 10 Gy and Dmax < 17 Gy will be considered acceptable. Deviations of D100% > 10 Gy and Dmax > 17 Gy will be considered unacceptable
Hopkins Verbal Learning Test revised (HVLT) and the FACT-Br QoL will be utilised pre treatment and at visits 1 and 10 and then at 3, 6, 9 and 12 months post radiotherapy
Intervention code [1] 296909 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300797 0
The primary endpoint will be neurocognitive function as assessed by the Hopkins Verbal Learning Test revised - Delayed Recall (HVLT DR).
Timepoint [1] 300797 0
12 months after the completion of radiotherapy
Secondary outcome [1] 330885 0
quality of life as assessed by the Functional Assessment of Cancer Therapy – Brain (FACT Br)
Timepoint [1] 330885 0
12 months post completion of radiotherapy treatment
Secondary outcome [2] 330924 0
Overall survival
Timepoint [2] 330924 0
12 months post completion of radiotherapy treatment
Secondary outcome [3] 330925 0
clinical intracranial progression free survival
Timepoint [3] 330925 0
12 months post completion of radiotherapy treatment
Secondary outcome [4] 330926 0
adverse events as assessed by the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE)
The side effects of treatment are the similar to standard whole brain radiotherapy . You may have none, some or all of the effects listed below, and they may be mild, moderate or severe.

The side effects may include headache, nausea, vomiting, scalp irritation or redness, hair loss, tiredness, memory problems, difficulty thinking clearly, ear irritation with decreased hearing, eye damage or cataracts with the possibility of impaired vision and temporary worsening of tumour-like symptoms such as seizures or weakness. Rare but serious side effects include damage to normal brain tissue and a second new cancer caused by radiation
Timepoint [4] 330926 0
12 months post completion of radiotherapy treatment
Secondary outcome [5] 330927 0
Radiotherapy contouring time .
This will be measured by a stopwatch operated by the individual clinicians involved. The contouring time will start once the patient’s plan is opened in Pinnacle by the radiation oncologist and will be stopped once the plan is saved and closed. .
Timepoint [5] 330927 0
At completion of radiotherapy treatment
Secondary outcome [6] 331037 0
Radiotherapy planning time. The radiotherapy planning time will commence once the patient’s plan is opened in Pinnacle by the radiotherapist and will be stopped once the plan is saved and closed
Timepoint [6] 331037 0
At completion of radiotherapy treatment
Secondary outcome [7] 331038 0
Radiotherapy machine treatment time. The radiotherapy machine time will be measured by the radiation therapist each session, for ten sessions, from when the patient initially enters the treatment room to when they are escorted out. The clinicians involved will be permitted to pause the stopwatch for significant unrelated interruptions, which cannot be reasonably postponed
Timepoint [7] 331038 0
At completion of radiotherapy treatment

Eligibility
Key inclusion criteria
1) Signed informed consent
2) Pathologically proven diagnosis of breast cancer
3) Stage IV disease with brain metastases which are outside of a 5 mm margin around either hippocampus
4) Stable or responsive extracranial disease as assessed by the patient’s medical oncologist
5) ECOG 0-2
6) Suitable for treatment with WBRT
7) Non-pregnant women aged over 18 years
8) Patients able to sufficiently cooperate with the proposed study requirements
9) Brain metastases that have previously been managed with surgical resection or stereotactic radiosurgery are permitted
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Life expectancy anticipated to be equal to or less than 12 weeks
2) Brain metastases within a 5mm margin of either hippocampus
3) Leptomeningeal disease
4) Pregnant women or women of child bearing age who do not wish to use contraception during radiotherapy treatment
5) Patients with significant psychological or psychiatric comorbidity
6) All cytotoxic chemotherapy must be withheld from 21 days before starting HAT WBRT, during HAT WBRT delivery and for 30 days after delivery of HAT WBRT

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
As this is a plot study it is not expected to reach statistical significance but rather will be used to gain initial clinical data and to validate procedures to be used for a larger scale study. The sample size will be 25 patients. This will allow us to obtain a reasonable amount of data on the costs of treatment. It should also permit sufficient, though modest, data regarding neurocognitive function after accounting for a conservative assumed death rate of 40% at 4 months and 60% at 6 months. (9; 11) To obtain sufficient patient accrual we anticipate a study duration of 2 years.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/02/2017
Actual
1/08/2017
Date of last participant enrolment
Anticipated
1/02/2019
Actual
1/01/2019
Date of last data collection
Anticipated
3/02/2020
Actual
1/01/2019
Sample size
Target
25
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 15125 0
6014 - Wembley

Funding & Sponsors
Funding source category [1] 295378 0
Charities/Societies/Foundations
Name [1] 295378 0
Breast Cancer Research Centre WA
Country [1] 295378 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Genesis Care
Address
Genesis Care
Building 1, The Mill, 2 Huntley Street
Alexandria, Sydney, NSW 2015
Country
Australia
Secondary sponsor category [1] 294201 0
None
Name [1] 294201 0
Address [1] 294201 0
Country [1] 294201 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296713 0
Belberry
Ethics committee address [1] 296713 0
Bellberry Limited
129 Glen Osmond Road
Eastwood S.A. 5063
Ethics committee country [1] 296713 0
Australia
Date submitted for ethics approval [1] 296713 0
17/01/2017
Approval date [1] 296713 0
03/02/2017
Ethics approval number [1] 296713 0

Summary
Brief summary
This pilot study will gather preliminary data on the impact of Hippocampal Avoidance Technique for Whole Brain Radiotherapy on cognition and clinical feasibility for the treatment of brain metastases in patients with breast cancer

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, have pathologically proven diagnosis of breast cancer stage IV disease with brain metastases which are outside of a 5 mm margin around either hippocampus

Study details
Whole brain radiotherapy (WBRT) is effective in providing local control of brain metastases and thereby preserving overall neurocognitive function as well as quality of life. Unfortunately, an adverse effect of WBRT is an often rapid decline in certain neurocognitive functions, particularly memory. This has been correlated with radiation induced injury thought to be crucial to memory formation. The planning of the treatment encompass the whole brain excluding the hippocampal avoidance regions, defined as the hippocampus with a 5 mm expansion.

All participants will receive Whole Brain Radiotherapy using the Hippocampal Avoidance Technique of 10 radiotherapy sessions over a two-week period. The radiotherapy treatment will take approximately 5-10 minutes daily, however the total time in the department will be approximately an hour.

Participants will be followed-up for up to 12 months after the completion of radiotherapy treatment in order to determine feasibility, safety, clinical benefit, survival rates and quality of life. Participants will also be asked to complete short verbal and written questionnaires to assess memory function and quality of life. These will be done before radiotherapy, on completion of radiotherapy and at follow-up appointments at 3, 6, 9 and 12 months. A CT scan and MRI scan of the head will be arranged prior to treatment, for the purpose of planning the radiotherapy. A follow-up brain MRI scan will be arranged at 3 months and 9 months after radiotherapy or when clinically indicated. This is consistent with current standard practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71846 0
Dr Evan Ng
Address 71846 0
Perth Radiation Oncology Wembley
24 Salvado Road
Wembley WA 6014
Country 71846 0
Australia
Phone 71846 0
+61 (8) 6318 2800
Fax 71846 0
Email 71846 0
[email protected]
Contact person for public queries
Name 71847 0
Sophie Mepham
Address 71847 0
Genesis Cancer Care
Level 5
126 Wellington Parade
Melbourne VIC
3002
Country 71847 0
Australia
Phone 71847 0
+61 409612302
Fax 71847 0
Email 71847 0
[email protected]
Contact person for scientific queries
Name 71848 0
Evan Ng
Address 71848 0
Perth Radiation Oncology Wembley
24 Salvado Road
Wembley WA 6014
Country 71848 0
Australia
Phone 71848 0
+61 (8) 6318 2800
Fax 71848 0
Email 71848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.