Clinical trial NCT06611306: BEAT-Breast: Trial of DE-iPTV in Patients With Primary Breast Cancer With Brain Metastases Who Are Not Suitable for Stereotactic Radiotherapy.
Official title: BEAT-Breast - Improving Outcomes for Breast Cancer Patients With Brain Metastases: a Pilot Nonrandomised Single Arm Phase 2 Clinical Trial in Patients With Primary Breast Cancer With Brain Metastases Who Are Not Suitable for Stereotactic Radiotherapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Brain Metastases, Adult
Breast Cancer
Keywords: Radiotherapy
Brain metastases
Metastatic Breast Cancer
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University of Leicester
name: Centro Nacional de Investigaciones Oncologicas CARLOS III
name: East and North Hertfordshire NHS Trust
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Imperial College Healthcare NHS Trust
First posted: 2024-09-24
Enrollment: 42
Sex: ALL
Minimum age (years): 16
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomised interventional multi-centre feasibility trial in patients with brain metastases from breast cancer receiving dose escalated internal PTV (DE-iPTV) radiotherapy
Primary purpose: TREATMENT

Brief summary: The aim of this study is to demonstrate if it is possible to delivering a novel and modern radiotherapy approach (Dose Escalated internal PTV (DE-iPTV)) and to collect health related quality of life in patients whose breast cancer has spread to the brain (brain metastases) at 8 weeks post enrolling into the study.

The main questions that have been set out to to answer are:

* Is it possible to deliver the novel radiotherapy approach, DE-iPTV?
* Is it possible to measure health -related quality of life?
* What impact does the novel radiotherapy approach have on: patient's quality of life, control of the brain metastasis (control of the lesion) and steroid use?

Participants will:

* Receive 5 doses of radiotherapy
* Complete weekly quality of life (EQ-5D) assessments and medication (steroid) diaries (via telephone/ postal) until 12 weeks post enrolment
* Be reviewed in clinic with up-to-date MRI scans at 8, 12 and 24 weeks post-enrolment
* Complete a more detailed HRQoL panel of assessments will be assessed at baseline, 8 weeks, 12 weeks and 24 weeks post enrolment.

Detailed description: Brain metastases from breast cancer are a common, and devastating, complication with survival times of 3 - 5 months from diagnosis.

The main treatment approaches to brain metastases are surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy. However, it is known that most patients with brain metastases receive either whole-brain radiotherapy (WBRT) or no treatment, with relatively low rates of surgery and SRS. Since the commonest treatment in those who do have treatment is WBRT, the local team have developed an approach that is believed to be (possibly) more effective than WBRT. The objective is to evaluate this approach in patients who are not suitable to receive more aggressive treatment and who would otherwise receive WBRT. The local approach involves using a modern radiotherapy planning approach, combined with careful, intra-metastasis dose escalation (Dose Escalated internal PTV (DE-iPTV)) to deliver a higher dose to tumour, while delivering less dose to the brain. The combination of less dose to normal structures and more dose to the lesion will hopefully improve Health-related Quality of Life (HRQoL).

The aim of this study is to demonstrate the feasibility of delivering complex radiotherapy, dose escalated internal PTV (DE-iPTV), and measuring quality of life at 8 weeks post-enrolment for patients with brain metastases from breast cancer who would otherwise receive WBRT. An exploratory blood-based biomarker sample collection and analysis will be completed. Furthermore, linked national cancer data will be used to measure the number of patients currently offered WBRT, including survival costs and hospital admissions, and thus provide a baseline to estimate the impact of this novel approach.

Eligibility criteria: Inclusion Criteria

1. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up
2. Adult (aged 16+) patients, resident in the United Kingdom.
3. Histologically confirmed primary breast cancer with brain metastases on MRI imaging
4. The treating oncologist considers whole-brain radiotherapy to be the most suitable treatment outside of the trial.
5. Eastern Cooperative Oncology Group Performance status 0, 1 or 2
6. Able to respond to question about their quality of life, symptoms, and side effects remotely (via telephone assessments
7. Life expectancy from extra-cranial disease \>3 months

Exclusion Criteria

1. Leptomeningeal disease
2. "Miliary" pattern of metastases: patients with over 15 metastases are excluded (clinician-based assessment)
3. Cystic metastases
4. Previous whole or partial brain radiotherapy (previous surgery or SRS is acceptable)
5. Plan for hippocampal-sparing whole brain radiotherapy.
6. Unable to give informed consent.
7. Prognosis less than 3 months
8. Pregnant or nursing women
9. Unable to complete a brain MRI and/or known allergy to gadolinium.

Primary outcomes:
measure: Feasibility of delivering DE-iPTV and measuring health related quality of life questionnaire in patients with brain metastases from breast cancer to whom their treating clinician would normally offer whole brain radiotherapy
timeFrame: 8 weeks post-enrolment
Secondary outcomes:
measure: Lesional Response
timeFrame: 8 weeks
measure: Intracranial progression
timeFrame: 3 months
measure: Intracranial progression
timeFrame: 6 months
measure: Treatments
timeFrame: Within 6 months of enrolment
measure: Central Nervous System (CNS) Failures
timeFrame: Within 6 months of enrolment
measure: Neurological toxicities
timeFrame: Within 6 months of enrolment
measure: Health Related Quality of Life
timeFrame: Within 6 months of enrolment
measure: Time to deterioration in quality of life
timeFrame: Within 6 months of enrolment
measure: Symptom Burden
timeFrame: Within 6 months of enrolment
measure: Steroid usage
timeFrame: Within 6 months of enrolment
measure: Quality-Adjusted Life Year
timeFrame: Within 6 months of enrolment
measure: Overall survival
timeFrame: End of study
Other outcomes:
measure: Changes in blood-based biomarkers
timeFrame: 8 weeks
measure: Imaging Changes
timeFrame: Up to 6 months post enrolment
measure: Radiation Necrosis
timeFrame: Up to 6 months post enrolment
Locations:
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
References:
citation: Chen J, Sinclair G, Rozati H, Hill L, Pakzad-Shahabi L, Wang J, Calvez KL, Paddick I, Williams M. Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial. Radiother Oncol. 2022 May;170:176-183. doi: 10.1016/j.radonc.2022.02.011. Epub 2022 Feb 17.