Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens. (TRACE)
November 26, 2025 updated by: iOMEDICO AG
Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens: a Multicenter, International, Prospective, Non-interventional Study in Germany and Austria (TRACE)
The objective of this non-interventional study (NIS) is to evaluate tucatinib (TUKYSA®) combined with trastuzumab and capecitabine in adult patients with locally advanced or metastatic HER2-positive breast cancer who have been previously treated with at least two anti-HER2 treatment regimens in a real-world setting,
Study Overview
Detailed Description
TRACE will collect real-world data on the treatment of tucatinib/trastuzumab/capecitabine in a broad patient population including older patients and patients with more comorbidities as compared to the pivotal trial HER2CLIMB. In contrast to HER2CLIMB, TRACE will also include patients receiving tucatinib/trastuzumab/capecitabine during 1st and 2nd palliative therapy line who were primarily diagnosed with early breast cancer and therefore already have received two prior anti-HER2 based treatment regimens before enrollment. Until today, no reliable data is available for these patient population. TRACE will primarily focus on HRQoL using the validated EORTC QLQ C30 + QLQ-BR23 + EQ-5D-5L questionnaires. Further aims are to evaluate effectiveness and safety in distinct subgroups focusing on effectiveness of tucatinib/trastuzumab/capecitabine in patients who have experienced prior therapies with trastuzumab and neratinib or capecitabine and HER2-targeted TKIs in the neoadjuvant, adjuvant or palliative setting, respectively.
Study sites may retrospectively include patients within 9 weeks (corresponds to 3 cycles) after start of study treatment up to 6 months after activation of respective site. Retrospectively included patients may have already completed study treatment or may have already deceased at the time of inclusion.
Study Type
Observational
Enrollment (Actual)
49
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Adult patients with locally advanced or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been previously treated with at least two prior anti-HER2 treatment regimens and with decision for treatment with tucatinib (TUKYSA®) in combination with trastuzumab and capecitabine.
Description
Inclusion Criteria:
- Aged 18 years or older.
- Histologically confirmed HER2+ breast cancer with HER2 positivity defined as a 3+ score by immunohistochemistry (IHC) or a positive result by in situ hybridization (ISH), optionally combined with a IHC2+ score.
- Diagnosis of locally advanced or metastatic HER2+ breast cancer, including patients with brain metastases.
- Prior treatment with at least two prior anti-HER2-based regimens.
Decision for treatment with tucatinib in combination with trastuzumab and capecitabine according to current SmPC of tucatinib either in
1st/2nd palliative treatment line (Cohort 1) or 3rd/4th palliative treatment line (Cohort 2).
- Progression after or intolerance of last systemic anti-HER2-based therapy.
- Indication for treatment with tucatinib as assessed by the treating physician.
- Signed written informed consent (only if patient is alive at time of inclusion, not applicable for retrospective inclusion of deceased patients).
- Knowledge of German language.
- Other criteria according to current SmPC of tucatinib
Exclusion Criteria:
- Contraindications according to SmPC of tucatinib
- Participation in an interventional clinical trial within 30 days prior to enrolment or simultaneous participation in an interventional clinical trial.
- Treatment with tucatinib/trastuzumab/capecitabine (=study treatment) in 5th or higher palliative therapy line.
- Onset of tucatinib treatment later than 22 days after start of therapy line (in case tucatinib administration is started later than trastuzumab and/or capecitabine for any reason)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Cohort 1
Patients receiving tucatinib/trastuzumab/capecitabine (=study treatment) in 1st or 2nd palliative therapy line.
|
tucatinib/trastuzumab/capecitabine according to TUKYSA® SmPC.
|
|
Cohort 2
Patients receiving tucatinib/trastuzumab/capecitabine (=study treatment) in 3rd or 4th palliative therapy line.
|
tucatinib/trastuzumab/capecitabine according to TUKYSA® SmPC.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to deterioration of EORTC global health scale by at least 10 points
Time Frame: Baseline, up to 24 months
|
Only for prospectively enrolled patients: Time to deterioration of EORTC global health scale is defined as the time interval between fill-in date of baseline questionnaire and the first decrease in global health scale score ≥ 10-point (compared to baseline).
If there was no such decrease, death will serve as event for this analysis, if occurring within 4 months after last filled-in questionnaire.
|
Baseline, up to 24 months
|
|
Changes in the global health scale
Time Frame: Baseline, up to 24 months
|
Only for prospectively enrolled patients: Changes in global health is provided by descriptive statistics of the EQ-5D-5L index value, the EQ-5D-5L visual analogue scale, the EORTC QLQ-C30 global health scale and all functional and symptom scores of the EORTC questionnaires.
|
Baseline, up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to next systemic treatment (TTNT)
Time Frame: Baseline, up to 5 years
|
TTNT (time to next systemic treatment) is defined as time from first administration of any study treatment (i.e., tucatinib/trastuzumab/capecitabine treatment) to start of a subsequent systemic antineoplastic therapy or death, whichever comes first.
|
Baseline, up to 5 years
|
|
Time to local intracranial treatment (TLT)
Time Frame: Baseline, up to 5 years
|
TLT (time to local intracranial treatment) is defined as time from first administration of any study treatment to start of a local intracranial therapy, end of a treatment interruption due to isolated intracranial progression, change of treatment strategy or death, whichever comes first.
It will be analyzed for patients with isolated intracranial progression after start of study treatment.
|
Baseline, up to 5 years
|
|
Overall response rate (ORR)
Time Frame: Baseline, up to 5 years
|
ORR is defined as proportion of patients with any response (partial or complete remission) overall.
|
Baseline, up to 5 years
|
|
Duration of response (DOR)
Time Frame: Baseline, up to 5 years
|
DOR is defined as time from first occurrence of any response (complete or partial remission) to progression or death, whichever comes first.
Analysis will be conducted in the subset of patients with any response.
|
Baseline, up to 5 years
|
|
Clinical benefit rate (CBR)
Time Frame: Baseline, up to 5 years
|
CBR is defined as proportion of patients with complete or partial remission for best response or with stable disease lasting for at least 24 weeks.
|
Baseline, up to 5 years
|
|
Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE
Time Frame: Baseline, up to 30 days after end of tucatinib treatment
|
Adverse events (AEs) and serious adverse events (SAEs) as characterized by type, frequency, severity and seriousness
|
Baseline, up to 30 days after end of tucatinib treatment
|
|
Therapy decision making
Time Frame: Baseline
|
Frequencies and percentages of parameters affecting therapy choice.
|
Baseline
|
|
Previous antineoplastic Therapies
Time Frame: Baseline
|
Frequency/type of previous systemic antineoplastic treatments (neoadjuvant/adjuvant/palliative)
|
Baseline
|
|
Previous anti-HER2 regimens
Time Frame: Baseline
|
Frequency and type of previous anti-HER2 based regimens
|
Baseline
|
|
Subsequent antineoplastic therapies
Time Frame: End of treatment, up to 5 years
|
Frequency and type of subsequent systemic antineoplastic therapies
|
End of treatment, up to 5 years
|
|
Local antineoplastic therapies
Time Frame: Baseline, up to 5 years
|
Frequency and type of local antineoplastic therapies (surgeries, radiotherapies) incl.
local intracranial therapies
|
Baseline, up to 5 years
|
|
Details on line of treatment for both cohorts
Time Frame: Baseline
|
Cohort 1: frequencies and percentages for line of treatment (1st-line or 2nd-line tucatinib treatment) Cohort 2: frequencies and percentages for line of treatment (3rd-line or 4th-line tucatinib treatment)
|
Baseline
|
|
Treatment Duration
Time Frame: Baseline, up to 5 years
|
Treatment duration of study treatment in total and per substance
|
Baseline, up to 5 years
|
|
Dose intensity
Time Frame: Baseline, up to 5 years
|
Dose intensity (absolute and relative) for each substance as prescribed by the treating physician
|
Baseline, up to 5 years
|
|
Dose modifications
Time Frame: Baseline, up to 5 years
|
Frequency, type and reasons of dose modifications (dose reductions, skipped administrations/delays/interruption) compared to SmPC of tucatinib for each substance.
|
Baseline, up to 5 years
|
|
Therapy management (use of relevant supportive medications)
Time Frame: Baseline, up to 5 years
|
Frequency of usage of antidiarrheal drugs for prophylaxis and treatment of tucatinib-induced diarrhea
|
Baseline, up to 5 years
|
|
Safety laboratory value: Aspartate aminotransferase (AST)
Time Frame: Baseline, up to 30 days after end of tucatinib treatment
|
During tucatinib administration, safety laboratory will be performed according to routine clinical practice.
Laboratory values of AST (Aspartate aminotransferase) measured will be documented continuously during tucatinib treatment.
Baseline levels of AST will be presented using descriptive statistics.
|
Baseline, up to 30 days after end of tucatinib treatment
|
|
Safety laboratory value: Alanine aminotransferase (ALT)
Time Frame: Baseline, up to 30 days after end of tucatinib treatment
|
During tucatinib administration, safety laboratory will be performed according to routine clinical practice.
Laboratory values of ALT (Alanine aminotransferase) measured will be documented continuously during tucatinib treatment.
Baseline levels of ALT will be presented using descriptive statistics.
|
Baseline, up to 30 days after end of tucatinib treatment
|
|
Safety laboratory value: bilirubin
Time Frame: Baseline, up to 30 days after end of tucatinib treatment
|
During tucatinib administration, safety laboratory will be performed according to routine clinical practice.
Laboratory values of bilirubin measured will be documented continuously during tucatinib treatment.
Baseline levels of bilirubin will be presented using descriptive statistics.
|
Baseline, up to 30 days after end of tucatinib treatment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of planned hospitalizations
Time Frame: Baseline, up to 5 years
|
Number of planned hospitalizations will be measured using descriptive statistics.
|
Baseline, up to 5 years
|
|
Duration of planned hospitalizations
Time Frame: Baseline, up to 5 years
|
Duration of planned hospitalizations will be measured using descriptive statistics.
|
Baseline, up to 5 years
|
|
Duration of sick leaves
Time Frame: Baseline, up to 5 years
|
Duration of sick leaves will be measured using descriptive statistics.
|
Baseline, up to 5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Anja Welt, PD Dr., Universitätsklinikum Essen, Innere Klinik (Tumorforschung)
- Study Chair: Rupert Bartsch, Assoc. Prof. PD Dr., Medical University of Vienna
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 21, 2022
Primary Completion (Actual)
June 30, 2025
Study Completion (Actual)
June 30, 2025
Study Registration Dates
First Submitted
February 1, 2022
First Submitted That Met QC Criteria
February 14, 2022
First Posted (Actual)
February 24, 2022
Study Record Updates
Last Update Posted (Estimated)
December 4, 2025
Last Update Submitted That Met QC Criteria
November 26, 2025
Last Verified
November 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IOM-120465
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.