Breast CancerGRADENCT07465172
GDF-15 and Its Relationship With Treatment-related ADverse Events in Breast Cancer
A study testing Blood collection for GDF-15 in people with Breast Cancer, run by Breast Cancer Trials, Australia and New Zealand at 4 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Blood collection for GDF-15
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Oct 2026to Oct 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 3 countries
Australia2 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Sherene Loi, Prof, +61 (03) 8559-5935, sherene.loi@petermac.org
Sherene Loi, Prof
Lake Macquarie Private Hospital
Newcastle, New South Wales, 2290
Nick Zdenkowski, Dr, +61 (02) 4942-2600, nick.zdenkowski@newcastle.edu.au
Nick Zdenkowski, Dr
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Michelle Li, Dr, +61 (0) 3 8559 5935, michelle.li@petermac.org
Michelle Li, Dr
Japan1 site
Okayama University Hospital
Okayama, 700-8558
Tadahiko Shien, Prof, +81 (08) 62357265, tshien@md.okayam-u.ac.jp
Tadahiko Shien, Prof
About this study
Official 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.
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Breast Cancer
- Being tested
- Blood collection for GDF-15
- Keywords
- GDF-15, T-DXd, Trastuzumab deruxtecan, Nausea, Vomiting, Weight loss, Adverse events
- Medical subject headings
- Breast Neoplasms, Nausea, Vomiting, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collection for GDF-15Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Blood Collection for GDF-15 | Other | Blood collection for GDF-15 during T-DXd treatment. Receives: Other: Blood collection for GDF-15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nausea prior to Cycle 3 of T-DXd, graded according to Common Terminology Criteria for Adverse Advents (CTCAE) v5.0.
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.
Measured: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).
Secondary outcomes (6)
Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
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.
Measured: 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.
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.
Measured: 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)
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.
Measured: From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days).
Progression-free survival (PFS)
To explore the relationship between baseline levels of GDF-15 and progression-free survival (PFS) on T-DXd
Measured: 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)
To explore the relationship between baseline levels of GDF-15 and time to treatment failure (TTF) on T-DXd.
Measured: 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
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
Measured: Prior to treatment commencement.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Multi-centre, prospective cohort study.
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Breast Cancer Trials, Australia and New Zealand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Heath Badger, Study director, Breast Cancer Trials, Australia and New ZealandSherene Loi, Prof, Study chair, Peter MacCallum Cancer Centre, AustraliaMichelle Li, Dr, Study chair, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07465172
- Sponsor's protocol ID
- BCT 2502
- Acronym
- GRADE
- Status last verified
- Sep 2026
- First submitted
- 26 Feb 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised Individual Patient Data (IPD) collected during the trial.
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT07465172
- Acronym / sponsor ID
- GRADE / BCT 2502
- Conditions
- Breast Cancer
- Keywords
- GDF-15, T-DXd, Trastuzumab deruxtecan, Nausea, Vomiting, Weight loss, Adverse events
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Breast Cancer Trials, Australia and New ZealandUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 11 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Multi-centre, prospective cohort study.
| Arm | Type | Receives |
|---|---|---|
| Blood Collection for GDF-15 | Other | Other: Blood collection for GDF-15Blood collection for GDF-15 during T-DXd treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood collection for GDF-15Blood 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. | Other | Blood Collection for GDF-15 |
Primary outcome
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.
6 secondary outcomes
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).
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).
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).
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.
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.
HER2 copy number
Time frame: Prior to treatment commencement.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Information about BCT 2502 GRADE will be available on the Open Trials section of the BCT website.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymised Individual Patient Data (IPD) collected during the trial.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Heath Badger study director
Breast Cancer Trials, Australia and New Zealand
Sherene Loi, Prof study chair
Peter MacCallum Cancer Centre, Australia
Michelle Li, Dr study chair
Peter MacCallum Cancer Centre, Australia
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood collection for GDF-15 in people with Breast Cancer, run by Breast Cancer Trials, Australia and New Zealand at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tracey Hay (+61 (0) 2 4925 5277, tracey.hay@bctrials.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.