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NCT Number: NCT07465172

GDF-15 and Its Relationship With Treatment-related ADverse Events in Breast Cancer

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.

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Key information

Conditions

Breast Cancer Body Weight Body Weight Changes Breast Diseases Breast Neoplasms Nausea Neoplasms Neoplasms by Site Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive Skin Diseases Skin and Connective Tissue Diseases Vomiting Weight Loss

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Lake Macquarie Private Hospital, Newcastle, New South Wales, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Current active reversible causes of decreased food intake, as determined by the Investigator.
  • Receiving tube feedings or any kind of parenteral nutrition at the time of enrolment into the study.
  • 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.
  • Current adherence to a calorie-restricted diet with the intention of weight loss.

Treatment and study plan

Blood collection for GDF-15

Other

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.

Primary outcomes

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

    Time frame: 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.

Secondary outcomes

  1. Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.

    Time frame: 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.

  2. Weight loss (cachexia) prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.

    Time frame: 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.

  3. Percentage change in GDF-15 and its correlation with treatment-related adverse events (TRAEs)

    Time frame: 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.

  4. Progression-free survival (PFS)

    Time frame: 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

  5. Time to treatment failure (TTF)

    Time frame: 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.

  6. HER2 copy number

    Time frame: 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

Other outcomes

  1. Exploratory: Association of baseline levels of GDF-15 with Treatment Related Adverse Events (TRAEs).

    Time frame: 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.

  2. Exploratory: Longitudinal change in weight after 2 cycles of T-DXd

    Time frame: 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.

  3. Exploratory: Longitudinal change in weight at end-of-treatment

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Michelle Li, Dr

CONTACT

[email protected]

+61 (0) 3 8559 5935

Tracey Hay

CONTACT

[email protected]

+61 (0) 2 4925 5277

Sponsors and collaborators

Lead sponsor

Breast Cancer Trials, Australia and New Zealand

Other

Registry information

Official study title

A Multi-centre, Prospective Cohort Study to Explore the Relationship Between Changes in GDF-15 Levels and Treatment-related Adverse Events During T-DXd Treatment in Breast Cancer Patients.

Acronym: GRADE

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Mar 11, 2026
Registry last updated
Mar 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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