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Brain Metastases, AdultPhase 2RAPPLENCT05050929

RAPid SimPLE Targeted Radiation Treatment for Brain Metastases

A Phase 2 study testing Targeting All Brain Metastases in people with Brain Metastases, Adult, run by British Columbia Cancer Agency at 6 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The aim of the study is to show that rapid, simple targeted radiotherapy to brain metastases with 8 Gy / 1 is non-inferior to 20 Gy / 5 in terms of overall survival for patients with poor prognosis. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Brain Metastases, Adult
What is being tested?
Targeting All Brain Metastases
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
6 sitesCanada
Study dates
1 Jul 2022to 30 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must fulfil all the following criteria to be eligible for admission to the study:
  • Age ≥ 18
  • Pathological diagnosis of a non-hematopoietic malignancy
  • Brain metastases of any size
  • Any number of untreated or progressing, previously treated brain metastases that can all be contoured and targeted
  • Presence of extracranial disease
Show all 11Show fewer
  • Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) ≤ 2.0 (https://brainmetgpa.com/) or Graded Prognostic Assessment ≤ 2.0 (Appendix I)
  • Able to complete the EuroQOL (EQ-5D-5L) questionnaire
  • Willing and able to have regular imaging follow up
  • Feasible to start protocol treatment within 14 calendar days of participant enrolment
  • Karnofsky Performance Score (KPS) ≥ 50

Who cannot join

  • Patients who fulfill any of the following criteria are not eligible for admission to the study:
  • Inability to have a brain MRI.
  • WBRT less than 3 months prior to randomization
  • Disseminated leptomeningeal carcinomatosis (limited pachymeningeal disease is permitted)
  • Multiple sclerosis
  • Neurologically declining despite corticosteroids
Show all 12Show fewer
  • Appropriate for surgery or stereotactic radiosurgery
  • Germ cell and primary brain tumours
  • Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
  • Any other serious intercurrent illness or medical condition judged by the local investigator to compromise the patient's safety, preclude safe administration of the planned protocol treatment, or prevent the patient from being managed according to the protocol guidelines
  • Pregnancy
  • Potentially fertile men or women of childbearing potential who are unwilling to employ highly effective contraception

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Canada6 sites

  • BC Cancer - Abbotsford

    Abbotsford British Columbia, British Columbia

  • BC Cancer - Kelowna

    Kelowna, British Columbia, V1Y5L3

  • BC Cancer - Prince George

    Prince George, British Columbia, V2M7E9

  • BC Cancer - Surrey

    Surrey, British Columbia

  • BC Cancer - Vancouver

    Vancouver, British Columbia, V5Z 4E6

  • BC Cancer - Victoria

    Victoria, British Columbia

Other trials in Canada

About this study

Official title: Randomized Phase II Non-Inferiority Study of 5-Day Versus 1-Day RAPid SimPLE (RAPPLE) Targeted Radiation Treatment for Brain Metastases

The aim of the study is to show that rapid, simple targeted radiotherapy to brain metastases with 8 Gy / 1 is non-inferior to 20 Gy / 5 in terms of overall survival for patients with poor prognosis.

Read the detailed description

Hypothesis For selected patients with limited life expectancy, a single targeted fraction of 8 Gy / 1 to brain metastases will provide equivalent survival as targeted radiotherapy with 20 Gy / 5 to brain metastases.

Justification The QUARTZ study randomized patients with brain metastases and poor prognosis between 20 Gy / 5 whole brain radiotherapy (WBRT) and best supportive care. The median survival in both arms of the study was 9 weeks. The quality of life in both arm was also the same. It is known that WBRT significantly diminishes quality of life. The investigators interpretation of the QUARTZ trial is that the unchecked growth of brain metastases in the best supportive care arm diminishes quality of life as much as WBRT. To control brain metastases without giving WBRT, targeted treatment with 20 Gy / 5 to the metastases alone is standard care at BC Cancer. Numerous randomized trials have compared the efficacy of 20-30 Gy / 5-10 fractions and 8 Gy / 1 for palliative treatment of pain from bone metastases. In addition, there is a randomized trial showing that 20 Gy / 5 and 8 Gy /1 are equally effective for the treatment of symptoms from spinal cord compression. This study will test the use of this shorter, one-visit treatment schedule against the standard 5-visit treatment schedule for patients with brain metastases.

Research Design Randomized Phase II Non-Inferiority Study. The estimated median survival for this cohort, based upon a prior cohort study from 2012-2016 at BC Cancer is 3 months (13 weeks). The investigators would regard a study median survival of less than the 9-week median survival observed in the QUARTZ trial as unacceptable. Hence, the hazard ratio for the experimental arm and the control arm is: 13 weeks / 9 weeks = 1.44. With one-sided Type I error set at alpha = 0.2 and power = 0.8, the investigators calculated a theoretical sample size of 86 patients. Based on prior experience with clinical trials for patients with brain metastases, a 15% risk of drop-out and loss to follow up is expected. Hence the final sample size will be 100 patients. Stratification by the diagnosis-specific graded prognostic assessment (DS-GPA) ranges of 0.0 - 1.0 and 1.5 - 2.0 and lung cancer versus other histologies will help to ensure baseline characteristics that predict for equal survival are equally distributed in both arms of the study.

Statistical Analysis The primary endpoint is overall survival. The study will be considered to be a positive phase II non-inferiority study if the median survival in the experimental arm is within 4 weeks of the median survival in the standard arm.

Being tested
Targeting All Brain Metastases
Keywords
radiotherapy, randomized clinical trial, phase II, non-inferiority, overall survival
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Targeting All Brain MetastasesRadiation

    Volumetric Modulated Arc Therapy

Study groups in NCT05050929
Study groupRoleWhat they receive
20 Gy in 5 Fractions Volumetric Modulated Arc Therapy to Brain MetastasesActive comparatorFive treatments of 4 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
Receives: Radiation: Targeting All Brain Metastases
8 Gy in 1 Fraction Volumetric Modulated Arc Therapy to Brain MetastasesExperimentalA single treatment of 8 Gy will be delivered using volumetric modulated arc therapy on a conventional linear accelerator in a conventional head shell without the use of stereotactic radiosurgery technique.
Receives: Radiation: Targeting All Brain Metastases

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Survival Time

    The median time from randomization to death

    Measured: 1 year

Secondary outcomes (7)

  1. Median Time to Decline in Karnofsky Performance Status

    The time from randomization to a 20-point decline in Karnofsky Performance Status

    Measured: 1 year

  2. Control of treated brain metastases

    Cumulative incidence of local recurrence of treated metastases

    Measured: 1 year

  3. Corticosteroid use

    Proportion of patients taking corticosteroids

    Measured: 6 weeks

  4. Control of brain disease

    Cumulative incidence of (local recurrence of treated metastases OR new metastases)

    Measured: 1 year

  5. Retreatments for brain metastases

    Proportion of patients with retreatment for brain metastases after radiotherapy

    Measured: 1 year

  6. Adverse Events

    Cumulative incidence of adverse events, graded using CTCAE Version 5.0

    Measured: 1 year

  7. Health-Related Quality of Life

    Median time to a minimum clinically important decline in Health-Related Quality of Life

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2021
  2. Study start1 Jul 2022
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Equal arms (1:1)
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05050929
Sponsor's protocol ID
H21-01343
Acronym
RAPPLE
Status last verified
Sep 2026
First submitted
4 Aug 2021
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. doi: 10.1016/S0140-6736(16)30825-X. Epub 2016 Sep 4.

    PubMed 27604504

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Targeting All Brain Metastases in people with Brain Metastases, Adult, run by British Columbia Cancer Agency at 6 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival Time (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05050929, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.

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