RAPid SimPLE Targeted Radiation Treatment for Brain Metastases
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Targeting All Brain Metastases.
- Who it may be relevant to
- Registry conditions: Brain Metastases, Adult. Basic parameters: 18 years — 100 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Randomized Phase II Non-Inferiority Study of 5-Day Versus 1-Day RAPid SimPLE (RAPPLE) Targeted Radiation Treatment for Brain Metastases
Overview
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.
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.
Interventions
- Radiation Targeting All Brain Metastases
Volumetric Modulated Arc Therapy
Primary outcome measures
- Survival Time [Time frame: 1 year]
Secondary outcome measures (7)
- Median Time to Decline in Karnofsky Performance Status [Time frame: 1 year]
- Control of treated brain metastases [Time frame: 1 year]
- Corticosteroid use [Time frame: 6 weeks]
- Control of brain disease [Time frame: 1 year]
- Retreatments for brain metastases [Time frame: 1 year]
- Adverse Events [Time frame: 1 year]
- Health-Related Quality of Life [Time frame: 1 year]
Eligibility criteria
Inclusion criteria
Subjects must meet all of the following criteria to be eligible for participation in this 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
- Diagnosis-Specific Graded Prognostic Assessment ≤ 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 days of participant enrolment
- Karnofsky Performance Score (KPS) ≥ 50
Exclusion criteria
Subjects are excluded from the study if any of the following criteria apply:
- 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
- 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 participant's safety, preclude safe administration of the planned protocol treatment, or prevent the participant 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Canada · 6 centers
- BC Cancer - Abbotsford — Abbotsford British Columbia
- BC Cancer - Kelowna — Kelowna
- BC Cancer - Prince George — Prince George
- BC Cancer - Surrey — Surrey
- BC Cancer - Vancouver — Vancouver
- BC Cancer - Victoria — Victoria
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 PMID 27604504
Identifiers
NCT: NCT05050929 · H21-01343