Tratamiento de radiación dirigida RAPid SIMPLE para metástasis cerebrales (RAPPLE)
Estudio de no inferioridad aleatorizado de fase II de tratamiento de radiación dirigida RAPid SimPLE (RAPPLE) de 5 días versus 1 día para metástasis cerebrales
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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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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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador activo: 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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Survival Time
Periodo de tiempo: 1 year
|
The median time from randomization to death |
1 year
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Median Time to Decline in Karnofsky Performance Status
Periodo de tiempo: 1 year
|
The time from randomization to a 20-point decline in Karnofsky Performance Status |
1 year
|
|
Control of treated brain metastases
Periodo de tiempo: 1 year
|
Cumulative incidence of local recurrence of treated metastases |
1 year
|
|
Corticosteroid use
Periodo de tiempo: 6 weeks
|
Proportion of patients taking corticosteroids |
6 weeks
|
|
Control of brain disease
Periodo de tiempo: 1 year
|
Cumulative incidence of (local recurrence of treated metastases OR new metastases) |
1 year
|
|
Retreatments for brain metastases
Periodo de tiempo: 1 year
|
Proportion of patients with retreatment for brain metastases after radiotherapy |
1 year
|
|
Adverse Events
Periodo de tiempo: 1 year
|
Cumulative incidence of adverse events, graded using CTCAE Version 5.0 |
1 year
|
|
Health-Related Quality of Life
Periodo de tiempo: 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
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- H21-01343
Información sobre medicamentos y dispositivos, documentos del estudio
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