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

NCT07465172 | Not Yet Recruiting

• 1 other identifier: BCT 2502
• Study Type: interventional
• Target: 150
• Locations: 3 countries
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

GDF-15; T-DXd; Trastuzumab deruxtecan; Nausea; Vomiting; Weight loss; Adverse events

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (6)

• 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).

• 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).

• 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).

• 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.

• 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.

Other Outcomes (3)

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

  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

  After receiving 2 cycles of T-DXd (each cycle is 28 days).

• Exploratory: Longitudinal change in weight at end-of-treatment

  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.

Study Arms (1)

Blood Collection for GDF-15

OTHER

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

Other: Blood collection for GDF-15

Interventions

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.

Blood Collection for GDF-15

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Breast Cancer Trials, Australia and New Zealand: lead

Study Sites (4)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Lake Macquarie Private Hospital

Newcastle, New South Wales, 2290, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Related Links

• Information about BCT 2502 GRADE will be available on the Open Trials section of the BCT website.

MeSH Terms

Conditions

Breast Neoplasms; Nausea; Vomiting; Weight Loss

Interventions

Growth Differentiation Factor 15

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes; Body Weight

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Growth Differentiation Factors; TGF-beta Superfamily Proteins; Proteins; Biological Factors

Study Officials

• Heath Badger

  Breast Cancer Trials, Australia and New Zealand

  STUDY DIRECTOR

• Sherene Loi, Prof

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

• Michelle Li, Dr

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-centre, prospective cohort study.

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 11, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will be made available for request after publication of the main/final study results; no end date.
• Access Criteria: 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).

Locations

US (1); AU (2); JP (1)