Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Blood Collection for GDF-15 | Other | Blood collection for GDF-15 during T-DXd treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood collection for GDF-15 | Other | Blood samples of 20-30mL (approximately 1-2 tablespoons in total) will be taken 4 times:
At each blood collection, participants will be asked about:
Personal and health information will also be collected from participants:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From baseline to after receiving 2 cycles of T-DXd treatment (each cycle is 28 days). |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory: Association of baseline levels of GDF-15 with Treatment Related Adverse Events (TRAEs). | 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). |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tracey Hay | Contact | +61 (0) 2 4925 5277 | tracey.hay@bctrials.org.au | |
| Michelle Li, Dr | Contact | +61 (0) 3 8559 5935 | michelle.li@petermac.org |
| Name | Affiliation | Role |
|---|---|---|
| Heath Badger | Breast Cancer Trials, Australia and New Zealand | Study Director |
| Sherene Loi, Prof | Peter MacCallum Cancer Centre, Australia | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
Not provided
| Label | URL |
|---|---|
| Information about BCT 2502 GRADE will be available on the Open Trials section of the BCT website. | View source |
Not provided
Anonymised Individual Patient Data (IPD) collected during the trial.
Data will be made available for request after publication of the main/final study results; no end date.
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).
Not provided
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009325 | Nausea |
| D014839 | Vomiting |
| D015431 | Weight Loss |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D055436 | Growth Differentiation Factor 15 |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Multi-centre, prospective cohort study.
Not provided
Not provided
Not provided
Not provided
|
| 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. | 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. | 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 | 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. | 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 | Prior to treatment commencement. |
| Exploratory: Longitudinal change in weight after 2 cycles of T-DXd | 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 | 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. |
| Michelle Li, Dr |
| Peter MacCallum Cancer Centre, Australia |
| Study Chair |
| Lake Macquarie Private Hospital | Newcastle | New South Wales | 2290 | Australia |
|
| Peter MacCallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
|
| Okayama University Hospital | Okayama | 700-8558 | Japan |
|
| D017437 |
| Skin and Connective Tissue Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D055412 | Growth Differentiation Factors |
| D055411 | TGF-beta Superfamily Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |