Whole Brain Radiotherapy (WBRT) Versus Stereotactic Radiosurgery (SRS) for 4 Upto 10 Brain Metastases (WBRTvsSRS)

May 29, 2020 updated by: Maastricht Radiation Oncology

Whole Brain Radiotherapy vs. Stereotactic Radiosurgery for 4 - 10 Brain Metastases:a Phase III Randomized Multicenter Trial

Recently stereotactic radiosurgery (SRS) in 5 up to 10 brain metastases showed to have equal survival as in 2 up to 4 brain metastases. Whole brain radiotherapy (WBRT) is currently the gold standard for patients with more than 3 brain metastases, but has significant side effects. In this prospective randomized phase III trial WBRT is compared to SRS for patients with 4 up to 10 BM.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Dutch guideline advices stereotactic radiosurgery (SRS) for patients with 1 up to 3 brain metastases (BM) and whole brain radiotherapy (WBRT) for patients with 4 or more BM. The interim analysis from the QUARTZ study showed that WBRT did not provide benefit in quality of life nor survival over best supportive care. WBRT has significant side effects, such as hair loss, fatigue, and cognitive dysfunction which may impair quality of life. A recently published study showed that SRS in patients with 5 up to 10 BM had a comparable survival to patients treated with 2 up to 4 BM. Many systemic therapies do not have a satisfactory intracranial response, because of the blood-brain barrier. The potential advantages of SRS i.e, limiting radiation doses to the uninvolved brain and a high rate of local tumour control by just a single treatment. Next logic step would be to compare WBRT with SRS alone in patients with 4-10 BM and evaluate whether SRS is superior to WBRT with regard to QOL.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081HV
        • VUMC
      • Amsterdam, Netherlands, 1105AZ
        • AMC
      • Den Haag, Netherlands, 2262BA
        • Haaglanden MC
      • Maastricht, Netherlands, 6202 AZ
        • Maastricht Radiation Oncology (MAASTRO clinic)
      • Rotterdam, Netherlands, 3015CE
        • Erasmus MC
      • Tilburg, Netherlands, 5042BS
        • Instituut Verbeeten
      • Vlissingen, Netherlands, 4382EK
        • ZRTI

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Minimal 4 up to a maximum of 10 BM on diagnostic MRI scan
  • Max diameter of single GTV 2.5cm
  • Max cumulative GTV of 30cm3
  • Karnofsky performance status ≥ 70
  • Any solid primary tumour. Small cell lung carcinoma, germinoma, and lymphoma are excluded
  • Ability to provide written informed consent

Exclusion Criteria:

  • Contra-indication for MRI
  • Prior treatment for BM (i.e. surgery, SRS or WBRT)
  • Concurrent use of systemic therapy
  • Maximum cumulative GTV of more than 30cm3 on planning-MRI
  • More than 10 BM on planning-MRI
  • A brainstem metastasis with a PTV of more than 20 cm3

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Stereotactic Radiosurgery
Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases:
Radiation: Stereotactic Radiosurgery
Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases
Other: Whole Brain Radiotherapy
Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases:
Radiation: Whole Brain Radiotherapy
Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Quality of life in patients with 4 - 10 brain metastases comparing WBRT and SRS
Time Frame: Change in quality of life measured from baseline to 3 months after radiotherapy
Quality of life is measured by the EQ-5D-5L, a descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)
Change in quality of life measured from baseline to 3 months after radiotherapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival steroid use (mg), toxicity including hair loss and fatigue.
Time Frame: 1 year
Overall survival
1 year
Time that patient is functioning independently (Karnofsky ≥ 70)
Time Frame: Change in Karnofsky index from baseline to 3 months after radiotherapy
Time that patient is functioning independently (Karnofsky ≥ 70)
Change in Karnofsky index from baseline to 3 months after radiotherapy
Steroid use
Time Frame: Change in steroid use from baseline to 3 months after radiotherapy
Steroid use in mg over time
Change in steroid use from baseline to 3 months after radiotherapy
Toxicity measured by hair loss and fatigue
Time Frame: Change in toxicity from baseline to 3 months after radiotherapy
Toxicity measured by hair loss and fatigue using CTCAE version 4.0
Change in toxicity from baseline to 3 months after radiotherapy
Degree of independence
Time Frame: Change in independence from baseline to 3 months after radiotherapy
Degree of independence of patients using the Barthel index
Change in independence from baseline to 3 months after radiotherapy

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Brain salvage during follow-up
Time Frame: 1 year
Brain salvage during follow-up, type of salvage, and time to salvage after randomisation
1 year
Verbal learning
Time Frame: Change in verbal recall and verbal recognition from baseline to 3 months after radiotherapy
Verbal recall and verbal regognition is measured using the Hopkins Verbal Learning Test - Revised
Change in verbal recall and verbal recognition from baseline to 3 months after radiotherapy
Quality of life of cancer patients
Time Frame: Change in Quality of life from baseline to 3 months after radiotherapy
QoL will be measured using the EORTC QLQ-C30
Change in Quality of life from baseline to 3 months after radiotherapy
Quality of life of cancer patients with brain neoplasms
Time Frame: Change in Quality of life from baseline to 3 months after radiotherapy
QoL will be measured using the EORTC QLQ-BN20
Change in Quality of life from baseline to 3 months after radiotherapy
Quality of life of cancer patients measuring cancer-related fatigue
Time Frame: Change in Quality of life from baseline to 3 months after radiotherapy
QoL will be measured using the EORTC QLQ-FA13
Change in Quality of life from baseline to 3 months after radiotherapy

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht Radiation Oncology

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

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 16, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 01-2015

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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