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GDF-15 e a sua Relação com Eventos Adversos Relacionados com o Tratamento no Cancro da Mama (GRADE)

28 de setembro de 2026 atualizado por: Breast Cancer Trials, Australia and New Zealand

Um Estudo de Coorte Prospectivo Multicêntrico para Explorar a Relação Entre Alterações nos Níveis de GDF-15 e Eventos Adversos Relacionados com o Tratamento Durante o Tratamento com T-DXd em Doentes com Cancro da Mama.

GRADE is trying to find out if there is a link between a hormone called GDF-15 and the side effects that people can experience when taking T-DXd.

GDF-15 can be measured in the blood. GDF-15 levels in the blood will go up when the body is stressed under certain conditions, including breast cancer. There is a link between high GDF-15 levels and the nausea and vomiting experienced with "morning sickness" in pregnancy. It has also been shown that GDF-15 levels will go up with the use of other types of chemotherapy that are known to cause nausea and vomiting.

Side effects such as feeling sick (nausea), vomiting and weight loss are common with T-DXd. Sometimes, these can be so severe that treatment needs to be stopped early. The investigators can't predict who will get bad side effects and who will not.

If the investigators can find out if there is a link between GDF-15 and the side effects of T-DXd, they can use this information in future clinical trials.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

Growth differentiation factor 15 (GDF-15), a stress-related hormone also known as macrophage inhibitory cytokine-1 (MIC-1), is a member of the transforming growth factor-beta (TGF-β) superfamily. It is not expressed under basal conditions but can be released in response to pro-inflammatory conditions such as obesity, insulin resistance, renal and heart failure, and malignancy.

Pre-clinical studies have established the role of elevated GDF-15 levels in tumour and platinum-based chemotherapy induced emesis and cachexia. It has also been proposed as a biomarker for all-cause mortality, as well as for poor prognoses in patients with cancer.

The hypothesis is that there is a positive correlation between increased levels of GDF-15 and the severity of treatment-related adverse events (particularly nausea, vomiting and cachexia) experienced by patients with breast cancer receiving T-DXd.

The aim of the study is to explore the relationship between relative change in levels of GDF-15 from baseline (pre-treatment) to after receiving T-DXd (post-C2 and at end of treatment) and the severity of treatment-related adverse events experienced by patients with breast cancer receiving T-DXd.

If a positive relationship is found with any or all of these objectives, then monoclonal antibodies inhibiting GDF-15 (such as ponsegromab or visugromab) may present a promising therapeutic and supportive option for patients receiving T-DXd.

Tipo de estudo

Intervencional

Inscrição (Estimado)

150

Estágio

  • Não aplicável

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.

Contato de estudo

Estude backup de contato

Locais de estudo

  • Austrália
    • New South Wales
      • Newcastle, New South Wales, Austrália, 2290
        • Lake Macquarie Private Hospital
        • Contato:
        • Investigador principal:
          • Nick Zdenkowski, Dr
    • Victoria
      • Melbourne, Victoria, Austrália, 3000
        • Peter MacCallum Cancer Centre
        • Contato:
        • Investigador principal:
          • Sherene Loi, Prof
  • Estados Unidos
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02215
        • Dana-Farber Cancer Institute
        • Contato:
        • Investigador principal:
          • Michelle Li, Dr
  • Japão
      • Okayama, Japão, 700-8558
        • Okayama University Hospital
        • Contato:
        • Investigador principal:
          • Tadahiko Shien, Prof

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. Participants aged ≥18 years.
  2. Histologically confirmed diagnosis of metastatic/advanced unresectable HER2-positive or HER2-low breast cancer.
  3. Planned to start treatment with T-DXd.
  4. Life expectancy of at least 4 months.

Exclusion Criteria:

  1. Current active reversible causes of decreased food intake, as determined by the Investigator.
  2. Receiving tube feedings or any kind of parenteral nutrition at the time of enrolment into the study.
  3. Ongoing cachexia attributable to other reasons unrelated to cancer or cancer treatment as determined by the Investigator that may confound interpretation of weight loss due to T-DXd.
  4. Current adherence to a calorie-restricted diet with the intention of weight loss.

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: Cuidados de suporte
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Outro: Blood Collection for GDF-15

Blood collection for GDF-15 during T-DXd treatment.
Outro: Blood collection for GDF-15

Blood samples of 20-30mL (approximately 1-2 tablespoons in total) will be taken 4 times:

  • Before first treatment with T-DXd
  • Two times during treatment (after the first and second doses of T-DXd); and
  • At the end of T-DXd treatment.

At each blood collection, participants will be asked about:

  • T-DXd side effects
  • Medications prescribe for T-DXd side effects
  • Weighed to see if their weight changes during treatment.

Personal and health information will also be collected from participants:

  • Date of birth and age, sex, ethnicity, height, weight, and activity levels.
  • Details about their cancer: diagnosis, type of cancer, other treatments, and pathology results.
  • Details about any previous pregnancies: how many, and the severity of any nausea or vomiting experienced during these pregnancies.
  • Details about their best response to treatment with T-DXd.
  • Details about the reason they stop T-DXd treatment.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Nausea prior to Cycle 3 of T-DXd, graded according to Common Terminology Criteria for Adverse Advents (CTCAE) v5.0.
Prazo: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).

To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade nausea (CTCAE Grade 2-4) experienced at this timepoint by patients with metastatic/advanced unresectable HER2-positive or HER2-low breast cancer.
From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
Prazo: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).

To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade vomiting (CTCAE Grade 2-4) experienced by patients at this timepoint.
From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).
Weight loss (cachexia) prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
Prazo: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).

To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade cachexia (CTCAE Grade 2-4) experienced by patients at this timepoint.
From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).
Percentage change in GDF-15 and its correlation with treatment-related adverse events (TRAEs)
Prazo: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).

To explore the correlation of the percentage change in levels of GDF-15 with the treatment-related adverse events (CTCAE Grade 2-4). Treatment-related adverse events (TRAEs) are adverse events classified as possibly, probably or definitely related to T-DXd treatment. TRAEs will be graded as per CTCAE v5.0.
From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).
Progression-free survival (PFS)
Prazo: Time from treatment start with T-DXd to the first occurrence of disease progression or death due to any cause, whichever came first, assessed up to 6 months.

To explore the relationship between baseline levels of GDF-15 and progression-free survival (PFS) on T-DXd
Time from treatment start with T-DXd to the first occurrence of disease progression or death due to any cause, whichever came first, assessed up to 6 months.
Time to treatment failure (TTF)
Prazo: Time from treatment start with T-DXd to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death, whichever came first, assessed up to 6 months.

To explore the relationship between baseline levels of GDF-15 and time to treatment failure (TTF) on T-DXd.
Time from treatment start with T-DXd to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death, whichever came first, assessed up to 6 months.
HER2 copy number
Prazo: Prior to treatment commencement.

To explore the relationship between HER2 copy number and change in levels of GDF-15. HER2 copy number determined by in-situ hybridization (ISH) on most recent available histopathology specimen or tumour/plasma genomic data (DNA/RNA), preferably in the metastatic setting
Prior to treatment commencement.

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Exploratory: Association of baseline levels of GDF-15 with Treatment Related Adverse Events (TRAEs).
Prazo: TRAEs occurring after Cycle 2, after Cycle 3 and within 30 days of end of treatment with T-DXd (each cycle is 28 days).

To explore if baseline levels of GDF-15 are associated with the incidence and severity of TRAEs experienced by patients on T-DXd, graded as per CTCAE v5.0.
TRAEs occurring after Cycle 2, after Cycle 3 and within 30 days of end of treatment with T-DXd (each cycle is 28 days).
Exploratory: Longitudinal change in weight after 2 cycles of T-DXd
Prazo: After receiving 2 cycles of T-DXd (each cycle is 28 days).

To explore if the longitudinal change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with trends in weight change. Weight change is measured as a percentage of baseline weight. End-of-treatment is defined as cessation of treatment due to disease progression or treatment toxicity.
After receiving 2 cycles of T-DXd (each cycle is 28 days).
Exploratory: Longitudinal change in weight at end-of-treatment
Prazo: At end-of-treatment with T-DXd; end-of-treatment is defined as cessation of treatment due to disease progression or treatment toxicity, whichever came first, assessed up to 6 months.

To explore if the longitudinal change in levels of GDF-15 from baseline at end-of-treatment with T-DXd is associated with trends in weight change. Weight change is measured as a percentage of baseline weight.
At end-of-treatment with T-DXd; end-of-treatment is defined as cessation of treatment due to disease progression or treatment toxicity, whichever came first, assessed up to 6 months.

Colaboradores e Investigadores

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

Patrocinador

Breast Cancer Trials, Australia and New Zealand

Investigadores

  • Diretor de estudo: Heath Badger, Breast Cancer Trials, Australia and New Zealand
  • Cadeira de estudo: Sherene Loi, Prof, Peter MacCallum Cancer Centre, Australia
  • Cadeira de estudo: Michelle Li, Dr, Peter MacCallum Cancer Centre, Australia

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Links úteis

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 (Estimado)

1 de outubro de 2026

Conclusão Primária (Estimado)

1 de outubro de 2028

Conclusão do estudo (Estimado)

1 de outubro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

26 de fevereiro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

9 de março de 2026

Primeira postagem (Real)

11 de março de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

30 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

28 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • BCT 2502

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

Anonymised Individual Patient Data (IPD) collected during the trial.

Prazo de Compartilhamento de IPD

Data will be made available for request after publication of the main/final study results; no end date.

Critérios de acesso de compartilhamento IPD

Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Applications will be subject to approval by Breast Cancer Trials concept@bctrials.org.au (refer to BCT Data Sharing Guidelines).

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • ANALYTIC_CODE

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

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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