Tratamento de radiação direcionada RAPid SimPLE para metástases cerebrais (RAPPLE)
Estudo randomizado de não inferioridade de fase II de tratamento de radiação direcionada de 5 dias versus 1 dia RAPid SimPLE (RAPPLE) para metástases cerebrais
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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British Columbia
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Abbotsford British Columbia, British Columbia, Canadá
- BC Cancer - Abbotsford
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Kelowna, British Columbia, Canadá, V1Y5L3
- BC Cancer - Kelowna
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Prince George, British Columbia, Canadá, V2M7E9
- BC Cancer - Prince George
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Surrey, British Columbia, Canadá
- BC Cancer - Surrey
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Vancouver, British Columbia, Canadá, V5Z 4E6
- BC Cancer - Vancouver
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Victoria, British Columbia, Canadá
- BC Cancer - Victoria
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
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
- 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
Exclusion Criteria
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
- 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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Comparador Ativo: 20 Gy in 5 Fractions Volumetric Modulated Arc Therapy to Brain Metastases
Five 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. |
Volumetric Modulated Arc Therapy |
|
Experimental: 8 Gy in 1 Fraction Volumetric Modulated Arc Therapy to Brain Metastases
A 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. |
Volumetric Modulated Arc Therapy |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Survival Time
Prazo: 1 year
|
The median time from randomization to death |
1 year
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Median Time to Decline in Karnofsky Performance Status
Prazo: 1 year
|
The time from randomization to a 20-point decline in Karnofsky Performance Status |
1 year
|
|
Control of treated brain metastases
Prazo: 1 year
|
Cumulative incidence of local recurrence of treated metastases |
1 year
|
|
Corticosteroid use
Prazo: 6 weeks
|
Proportion of patients taking corticosteroids |
6 weeks
|
|
Control of brain disease
Prazo: 1 year
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Cumulative incidence of (local recurrence of treated metastases OR new metastases) |
1 year
|
|
Retreatments for brain metastases
Prazo: 1 year
|
Proportion of patients with retreatment for brain metastases after radiotherapy |
1 year
|
|
Adverse Events
Prazo: 1 year
|
Cumulative incidence of adverse events, graded using CTCAE Version 5.0 |
1 year
|
|
Health-Related Quality of Life
Prazo: 1 year
|
Median time to a minimum clinically important decline in Health-Related Quality of Life |
1 year
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Alan Nichol, MD, BC Cancer Vancouver
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- H21-01343
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