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GDF-15 en de relatie met behandeling-gerelateerde bijwerkingen bij borstkanker (GRADE)

28 september 2026 bijgewerkt door: Breast Cancer Trials, Australia and New Zealand

Een multicenter, prospectieve cohortstudie om de relatie te onderzoeken tussen veranderingen in GDF-15-niveaus en behandeling-gerelateerde bijwerkingen tijdens T-DXd-behandeling bij borstkankerpatiënten.

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.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

150

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Australië
    • New South Wales
      • Newcastle, New South Wales, Australië, 2290
        • Lake Macquarie Private Hospital
        • Contact:
        • Hoofdonderzoeker:
          • Nick Zdenkowski, Dr
    • Victoria
      • Melbourne, Victoria, Australië, 3000
        • Peter MacCallum Cancer Centre
        • Contact:
        • Hoofdonderzoeker:
          • Sherene Loi, Prof
  • Japan
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
        • Contact:
        • Hoofdonderzoeker:
          • Tadahiko Shien, Prof
  • Verenigde Staten
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02215
        • Dana-Farber Cancer Institute
        • Contact:
        • Hoofdonderzoeker:
          • Michelle Li, Dr

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Ondersteunende zorg
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Ander: Blood Collection for GDF-15

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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Nausea prior to Cycle 3 of T-DXd, graded according to Common Terminology Criteria for Adverse Advents (CTCAE) v5.0.
Tijdsspanne: 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).

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
Tijdsspanne: 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.
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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.

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Exploratory: Association of baseline levels of GDF-15 with Treatment Related Adverse Events (TRAEs).
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Breast Cancer Trials, Australia and New Zealand

Onderzoekers

  • Studie directeur: Heath Badger, Breast Cancer Trials, Australia and New Zealand
  • Studie stoel: Sherene Loi, Prof, Peter MacCallum Cancer Centre, Australia
  • Studie stoel: Michelle Li, Dr, Peter MacCallum Cancer Centre, Australia

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 oktober 2026

Primaire voltooiing (Geschat)

1 oktober 2028

Studie voltooiing (Geschat)

1 oktober 2028

Studieregistratiedata

Eerst ingediend

26 februari 2026

Eerst ingediend dat voldeed aan de QC-criteria

9 maart 2026

Eerst geplaatst (Werkelijk)

11 maart 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

30 september 2026

Laatste update ingediend die voldeed aan QC-criteria

28 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • BCT 2502

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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

IPD-tijdsbestek voor delen

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

IPD-toegangscriteria voor delen

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).

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • ANALYTIC_CODE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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