BEAT-Breast: Trial of DE-iPTV in Patients With Primary Breast Cancer With Brain Metastases Who Are Not Suitable for Stereotactic Radiotherapy. (BEAT-Breast)

October 10, 2024 updated by: Imperial College London

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DE-iPTV radiotherapy
Patients will undergo a radiotherapy planning scan, and an upto date MRI brain with contrast. Patients will receive 5 fractions of DE-iPTV radiotherapy over 1 week.
Radiation: DE-iPTV
Dose-escalated VMAT-based radiotherapy, as previously described in our planning study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 8 weeks post-enrolment
Completion of radiotherapy and completion of EuroQol- 5 Dimension (EQ-5D-5L) questionnaire
8 weeks post-enrolment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lesional Response
Time Frame: 8 weeks
Lesional response and intracranial progression measured using RANO-BM criteria
8 weeks
Intracranial progression
Time Frame: 3 months
Intracranial progression based on RANO-BM
3 months
Intracranial progression
Time Frame: 6 months
Intracranial progression based on RANO-BM
6 months
Treatments
Time Frame: Within 6 months of enrolment
Use of further brain-directed therapies (reported by clinician)
Within 6 months of enrolment
Central Nervous System (CNS) Failures
Time Frame: Within 6 months of enrolment
Time to CNS failure (either lesional progression or developing a new lesion as per RANO-BM)
Within 6 months of enrolment
Neurological toxicities
Time Frame: Within 6 months of enrolment
Acute and late neurological/ CNS toxicity as assessed using CTCAE v5
Within 6 months of enrolment
Health Related Quality of Life
Time Frame: Within 6 months of enrolment
HRQoL over time (participants reported outcomes for descriptive analysis)
Within 6 months of enrolment
Symptom Burden
Time Frame: Within 6 months of enrolment
Symptom burden assessed by collection of clinician-recorded toxicities
Within 6 months of enrolment
Steroid usage
Time Frame: Within 6 months of enrolment
Use of corticosteroids over time, assessed through clinician reports and patient diaries
Within 6 months of enrolment
Quality-Adjusted Life Year
Time Frame: Within 6 months of enrolment
Quality-Adjusted Life Year
Within 6 months of enrolment
Overall survival
Time Frame: End of study
Overall survival
End of study
Time to deterioration in quality of life
Time Frame: Within 6 months of enrolment
Time to deterioration in Health Related Quality of Life - measured as time to first time there is a minimum clinically significant change in EuroQol- 5 Dimension (EQ-5D-5L)
Within 6 months of enrolment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in blood-based biomarkers
Time Frame: 8 weeks
Change between baseline and week 8 levels of Circulating Tumour DNA (ctDNA) and S100
8 weeks
Imaging Changes
Time Frame: Up to 6 months post enrolment
MRI-based response (as per RANO-BM and serial volumetric measurements)
Up to 6 months post enrolment
Radiation Necrosis
Time Frame: Up to 6 months post enrolment
Radiation necrosis based on radiologist report
Up to 6 months post enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Norfolk and Norwich University Hospitals NHS Foundation Trust
East and North Hertfordshire NHS Trust
University of Leicester
Imperial College Healthcare NHS Trust
Centro Nacional de Investigaciones Oncologicas CARLOS III

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 6, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 23, 2024

First Submitted That Met QC Criteria

September 23, 2024

First Posted (Actual)

September 24, 2024

Study Record Updates

Last Update Posted (Actual)

October 15, 2024

Last Update Submitted That Met QC Criteria

October 10, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C/46/2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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