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Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases (CORE)

20 de agosto de 2019 atualizado por: Royal Marsden NHS Foundation Trust

A Randomised Trial of Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases

Metastatic spread of cancer from its primary site to distant organs is the commonest cause of death from cancer. The term oligometastases describes an intermediate metastatic state, in which cancer exists as a limited number of metastases at first, before cells acquire the ability to metastasise more widely. For the large majority of solid cancers, once metastatic disease has been diagnosed the chances of cure are small. There are several situations where this is not the case, but it is not known if stereotactic body radiotherapy (SBRT) for oligometastatic disease will alter outcomes or whether the toxicity burden of this treatment is justified. SBRT is targeted radiotherapy which destroys cancer cells in the area of the body it is aimed at however low dose radiation may be received by surrounding tissue.

It is difficult to quantify incidence of patients with multiple primary cancers developing at intervals that are representative of oligometastatic stage IV disease, (defined for the purposes of this trial as ≤ 3 metastatic sites). However an increase in the use of surveillance imaging, together with improved diagnostic sensitivity has led to the diagnosis of patients with asymptomatic oligometastatic relapse becoming a more common clinical occurrence. The CORE study is a randomized controlled trial that will be conducted in patients with cancer in one of three primary sites where oligometastatic disease relapse is a common clinical scenario: breast, prostate and non-small cell lung cancer (NSCLC). The study will evaluate the use of SBRT in this patient population.

Eligible patients who consent to participate in this clinical trial will be randomized to receive standard care or standard care plus SBRT we hope to recruit approximately 206 patients to the study and the primary outcome measure is progression free survival.

Visão geral do estudo

Status

Ativo, não recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

CORE is a phase II/III, multi-centre, non-blinded, parallel group randomised controlled trial in patients with breast, prostate or NSCLC primary cancer comparing standard of care (SOC) with or without SBRT for extra-cranial metastases. The aim of the phase II study is to demonstrate 1) feasibility of recruitment, 2) deliverability of the study in a multi-centre setting and 3) activity of SBRT, based on progression free survival, across the three tumour types. If all three aims are achieved the trial will be amended to roll into parallel tumour-site specific phase III trials.

Eligible patients are those with either primary breast, prostate or NSCLC who have presented with ≤3 extra-cranial, metachronous, oligometastases, all suitable for SBRT. Patients will be randomised in a 1:1 ratio to either SOC or SOC with the addition of SBRT. Choice of SOC treatment is at the discretion of the local oncologist and defined per patient prior to randomisation (see section 8). Patients randomised to SBRT+SOC will receive a dose and fractionation regimen dependent on the metastatic site and proximity to dose limiting organs and normal tissues. Treatment will take place within 6 weeks of randomisation. The average scheme would be 3 treatments over 5 days but the maximum period of SBRT duration could be 8 treatments over 19 days.

All patients will be reviewed every 3 months with a clinical examination and tumour markers (where applicable) during years 1 and 2, and 6 monthly thereafter to 5 years. Staging and follow up imaging protocols will be tumour type dependent:

  • Breast: 3 monthly CT scans for years 1 and 2, and 6 monthly thereafter to 5 years.
  • NSCLC: 3 monthly CT scans for years 1 and 2, 6 monthly to year 3, then annually to 5 years.
  • Prostate: CT scans will be performed at 6, 12 and 24 months with imaging triggered by appropriate PSA rises. A rising PSA defined as 2 successive PSA rises from nadir, measured a minimum of 4 weeks apart. If the overall PSA rise has a doubling time of ≥ 3 months or the PSA level has doubled the original PSA value at trial entry or if clinically indicated, then restaging should be considered.

All patients will have a toxicity assessment at each clinic visit and patient reported quality of life (QOL) assessment at 3, 6, 12, 18 and 24 months.

Tipo de estudo

Intervencional

Inscrição (Real)

245

Estágio

  • Fase 2
  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Austrália
    • New South Wales
      • Liverpool, New South Wales, Austrália
        • Liverpool Hospital
      • Waratah, New South Wales, Austrália
        • Calvary Mater Newcastle
    • Queensland
      • Brisbane, Queensland, Austrália
        • Royal Brisbane and Women's Hospital
      • Brisbane, Queensland, Austrália
        • Princess Alexandra Hospital
    • South Australia
      • Adelaide, South Australia, Austrália
        • Royal Adelaide Hospital
      • Adelaide, South Australia, Austrália
        • GenesisCare - Adelaide Radiotherapy Centre
    • Victoria
      • Melbourne, Victoria, Austrália
        • Austin Health
      • Melbourne, Victoria, Austrália
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Nedlands, Western Australia, Austrália
        • Sir Charles Gairdner Hospital
  • Reino Unido
      • Belfast, Reino Unido
        • Belfast City Hospital
      • Birmingham, Reino Unido
        • Queen Elizabeth Hospital
      • Bristol, Reino Unido
        • Bristol Haematology and Oncology Centre
      • Cambridge, Reino Unido
        • Addenbrooke's Hospital
      • Glasgow, Reino Unido
        • The Beatson
      • Guildford, Reino Unido
        • Royal Surrey County Hospital
      • Leeds, Reino Unido
        • St James's University Hospital
      • Leicester, Reino Unido
        • Leicester Royal Infirmary
      • London, Reino Unido, SW3 6JJ
        • Royal Marsden Hospital
      • London, Reino Unido
        • University College Hospital
      • London, Reino Unido
        • St Bartholomew's Hospital
      • London, Reino Unido
        • Guy's Hospital
      • Manchester, Reino Unido
        • The Christie Hospital
      • Middlesborough, Reino Unido
        • James Cook University Hospital
      • Newcastle upon Tyne, Reino Unido
        • Freeman Hospital
      • Nottingham, Reino Unido
        • Nottingham City Hospital
      • Sheffield, Reino Unido
        • Weston Park Hospital
      • Sutton, Reino Unido
        • Royal Marsden Hospital
      • Wirral, Reino Unido
        • Clatterbridge Cancer Centre
    • Oxfordshire
      • Oxford, Oxfordshire, Reino Unido
        • Churchill Hospital
    • Surrey
      • London, Surrey, Reino Unido, HA6 2RN
        • Mount Vernon Cancer Centre

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion criteria

  1. Age ≥ 18 years
  2. WHO performance status 0-2
  3. Histological confirmation of primary malignancy (histological confirmation of metastasis is not mandatory but should be performed in any situation where there is diagnostic uncertainty). Patients with breast, NSCLC or prostate primary malignancies are eligible.
  4. Predicted life expectancy > 6 months
  5. ≤ 3 metastatic lesions (total). A maximum of 2 different organ systems (e.g. liver, lung, bone, nodal) may contain metastases but the total number of lesions must not exceed 3. For example, a patient with 3 liver metastases or 1 liver metastasis and 2 lung metastases would be eligible. A patient with 1 lung metastasis, 1 liver metastasis and an adrenal metastasis is ineligible.
  6. All metastases must be visible, imaging defined targets and be suitable for treatment with SBRT in accordance with the dose fractionation options specified in the protocol. (See the associated CORE trial radiotherapy delivery guidelines for detailed SBRT guidance by metastatic site)
  7. Patients who have received prior ablative therapy (e.g. surgery, RFA or SBRT) for metastatic disease are eligible, as long as this site is controlled on imaging at the point of trial entry and the total number of metastases over time since diagnosis of metastatic disease does not exceed 3. Patients with 2 or 3 metastases in which ablative therapy (e.g. surgery/RFA) to 1 site is deemed appropriate as part of standard therapy may be entered into the trial following successful delivery of the ablative treatment. Ablative therapy (e.g. surgery, RFA, cryoablation, SBRT) is not permissible as a standard of care option following randomisation for patients as part of the trial.

  8. Only patients with metachronous metastatic disease presentation are eligible. Primary site must be controlled.

    NSCLC patients with synchronous presentation of a single brain metastasis with the primary lung malignancy are eligible as long as both sites of disease have received radical treatment. Both primary lung site and solitary synchronous brain metastasis must be controlled at trial entry, and the total number of metastases over time including the brain metastasis must not exceed 3.

    Permissible disease-free intervals are:

    Breast: ≥ 6 months from completion of radical treatment including any adjuvant therapy to diagnosis of metastases. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible.

    NSCLC: ≥ 4 months from completion of radical treatment (not including any adjuvant chemotherapy) to diagnosis of metastases.

    Prostate: ≥ 6 months from completion of radical treatment including any adjuvant therapy to diagnosis of metastases. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible.

  9. Only patients who are systemic therapy naïve in the metastatic setting are eligible. Prior systemic therapy in the adjuvant setting is permitted. Patients who have had a change in endocrine therapy due to the diagnosis of oligometastatic disease can be entered into the CORE trial as long as entry is within 8 weeks of this change in therapy for prostate cancer patients and within 10 weeks of this change in therapy for breast cancer patients.
  10. Adequate baseline organ function to allow SBRT to all relevant targets dependent on location of metastatic subsite
  11. Negative pregnancy test (for women of childbearing potential)
  12. Written informed consent.

Exclusion criteria

  1. Intra-cranial metastases (not meeting above inclusion criterion 8).
  2. Malignant pleural effusion
  3. Malignant peritoneal disease
  4. Any single metastasis >6cm,( >5cm for lung metastases)
  5. Prior radiotherapy to a site that precludes safe delivery of SBRT
  6. Co-morbidities precluding staging or follow up imaging, or precluding procedures required to facilitate SBRT
  7. Loco-regional nodal relapse where surgery is considered the standard of care and is technically feasible. Patients with internal mammary chain or supraclavicular fossa lymph node relapses of breast cancer are eligible if SBRT dose constraints can be met. Patients with axillary nodal relapse from breast cancer are excluded
  8. Spinal cord compression, or impingement of the cord or any other situation whereby the clinician feels that urgent radiotherapy to the spine is required (within 24 hours)
  9. Any condition or significant clinical co-morbidities that preclude the safe delivery of SBRT (e.g. history of clinically significant diffuse interstitial lung disease if SBRT to lung metastases or lesions adjacent to lungs are considered or clinically significant colitis i.e. ulcerative colitis /Crohn's disease if SBRT to the pelvis or abdomen is considered).
  10. Prostate cancer patients who have relapsed on Androgen Deprivation Therapy (ADT) which was started for biochemical relapse without staging investigations to define their relapse status, or who have relapsed on CAB which was started for biochemical relapse.
  11. Prostate cancer patients receiving or have previously received abiraterone, enzalutamide or chemotherapy e.g. docetaxel.
  12. Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival.
  13. Patients whose entry to the trial will cause unacceptable clinical delays to their planned management.
  14. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

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: Standard of Care
Standard of care (SOC) is at the discretion of the local oncologist.
Outro: Standard of Care
Choice of standard of care treatment at the discretion of the local oncologist. This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy
Experimental: Standard of Care + SBRT
Patients randomised to SBRT will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC.
Outro: Standard of Care
Choice of standard of care treatment at the discretion of the local oncologist. This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy
Radiação: SBRT
Patients will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC. All patients should commence SOC therapy within 4 weeks of completing SBRT treatment.
Outros nomes:
  • SABR
  • Stereotactic body Radiotherapy

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Progression Free Survival
Prazo: 60 months post treatment
Time from randomisation to evidence of progression of cancer at any site or death from any cause
60 months post treatment

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Feasibility of recruitment
Prazo: 3 years from first patient
Recruitment rate and proportion of patients receiving SBRT (if allocated) in the absence of new developing widespread disease
3 years from first patient
Feasibility of SBRT delivery
Prazo: 3 years from first patient
Recruitment of patients receiving SBRT within the dosimetric constraints
3 years from first patient
Overall Survival
Prazo: 60 months post treatment
Time from randomisation until time of death from any cause
60 months post treatment
Local lesion control
Prazo: 60 months post treatment
Time from randomisation until radiological evidence of progression at the treated site and be measured on a lesion based on analysis using RECIST criteria.
60 months post treatment
Clinical reported acute and late toxicity
Prazo: 60 months post treatment
Clinician reported acute and late toxicity will be graded using NCI CTCAE v4.0 / RTOG systems. Acute events are defined as those occurring up to 3 months follow-up; late events are reported from 6 months post randomisation.
60 months post treatment
Patient reported Quality of Life
Prazo: Pre-treatment and at 3,6,12,18 and 24 months post treatment
Patient reported quality of life will be measured using EORTC QLQ C30
Pre-treatment and at 3,6,12,18 and 24 months post treatment

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Freedom from widespread metastatic disease (FFWMD)
Prazo: Pre-treatment and at 3,6,9,12,15,18,21,24,30,36,42,48,54 and 60 months post treatment
FFWMD will be measured from the time of randomisation until radiological evidence of disease progression, which is not suitable for radical salvage therapy.
Pre-treatment and at 3,6,9,12,15,18,21,24,30,36,42,48,54 and 60 months post treatment

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Royal Marsden NHS Foundation Trust

Colaboradores

Institute of Cancer Research, United Kingdom
National Health Service, United Kingdom

Investigadores

  • Investigador principal: Vincent Khoo, MD, Royal Marsden NHS Foundation Trust

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de novembro de 2016

Conclusão Primária (Antecipado)

1 de outubro de 2024

Conclusão do estudo (Antecipado)

1 de outubro de 2024

Datas de inscrição no estudo

Enviado pela primeira vez

26 de abril de 2016

Enviado pela primeira vez que atendeu aos critérios de CQ

28 de abril de 2016

Primeira postagem (Estimativa)

3 de maio de 2016

Atualizações de registro de estudo

Última Atualização Postada (Real)

21 de agosto de 2019

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de agosto de 2019

Última verificação

1 de agosto de 2019

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CCR4323
  • 182152 (Outro identificador: IRAS)
  • ISRCTN45961438 (Identificador de registro: ISRCTN)

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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