Breast Cancer
Conditions
Keywords
GDF-15, T-DXd, Trastuzumab deruxtecan, Nausea, Vomiting, Weight loss, Adverse events
Brief 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. 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.
Interventions
OTHERBlood 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.
Sponsors
Breast Cancer Trials, Australia and New Zealand
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Multi-centre, prospective cohort study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nausea prior to Cycle 3 of T-DXd, graded according to Common Terminology Criteria for Adverse Advents (CTCAE) v5.0. | 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
| Measure | Time frame | Description |
|---|---|---|
| Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0. | 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. |
| Weight loss (cachexia) prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0. | 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. |
| Percentage change in GDF-15 and its correlation with treatment-related adverse events (TRAEs) | 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. |
| Progression-free survival (PFS) | 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 to treatment failure (TTF) | 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. |
| HER2 copy number | 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 |
Countries
Australia, Japan, United States
Contacts
CONTACTTracey Hay
CONTACTMichelle Li, Dr
STUDY_DIRECTORHeath Badger
Breast Cancer Trials, Australia and New Zealand
STUDY_CHAIRSherene Loi, Prof
Peter MacCallum Cancer Centre, Australia
STUDY_CHAIRMichelle Li, Dr
Peter MacCallum Cancer Centre, Australia
Outcome results
None listed