Clinical trial NCT05253911: Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens.
Official title: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HER2-positive Breast Cancer
Keywords: HER2-positive breast cancer
Tucatinib
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2022-02-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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,

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Time to deterioration of EORTC global health scale by at least 10 points
timeFrame: Baseline, up to 24 months
measure: Changes in the global health scale
timeFrame: Baseline, up to 24 months
Secondary outcomes:
measure: Time to next systemic treatment (TTNT)
timeFrame: Baseline, up to 5 years
measure: Time to local intracranial treatment (TLT)
timeFrame: Baseline, up to 5 years
measure: Overall survival (OS)
timeFrame: Baseline, up to 5 years
measure: Overall response rate (ORR)
timeFrame: Baseline, up to 5 years
measure: Duration of response (DOR)
timeFrame: Baseline, up to 5 years
measure: Clinical benefit rate (CBR)
timeFrame: Baseline, up to 5 years
measure: Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE
timeFrame: Baseline, up to 30 days after end of tucatinib treatment
measure: Safety laboratory value: Aspartate aminotransferase (AST)
timeFrame: Baseline, up to 30 days after end of tucatinib treatment
measure: Safety laboratory value: Alanine aminotransferase (ALT)
timeFrame: Baseline, up to 30 days after end of tucatinib treatment
measure: Safety laboratory value: bilirubin
timeFrame: Baseline, up to 30 days after end of tucatinib treatment
measure: Therapy decision making
timeFrame: Baseline
measure: Previous antineoplastic Therapies
timeFrame: Baseline
measure: Previous anti-HER2 regimens
timeFrame: Baseline
measure: Subsequent antineoplastic therapies
timeFrame: End of treatment, up to 5 years
measure: Local antineoplastic therapies
timeFrame: Baseline, up to 5 years
measure: Details on line of treatment for both cohorts
timeFrame: Baseline
measure: Treatment Duration
timeFrame: Baseline, up to 5 years
measure: Dose intensity
timeFrame: Baseline, up to 5 years
measure: Dose modifications
timeFrame: Baseline, up to 5 years
measure: Therapy management (use of relevant supportive medications)
timeFrame: Baseline, up to 5 years
Other outcomes:
measure: Number of planned hospitalizations
timeFrame: Baseline, up to 5 years
measure: Duration of planned hospitalizations
timeFrame: Baseline, up to 5 years
measure: Duration of sick leaves
timeFrame: Baseline, up to 5 years
Locations:
city: Vienna
country: Austria
facility: Medizinische Universität Wien, Innere Medizin I, Hämatologie und Onkologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Innere Klinik (Tumorforschung)
state: Northrhine-Westphalia
Study officials:
affiliation: Universitätsklinikum Essen, Innere Klinik (Tumorforschung)
name: Anja Welt, PD Dr.
role: STUDY_CHAIR
affiliation: Medical University of Vienna
name: Rupert Bartsch, Assoc. Prof. PD Dr.
role: STUDY_CHAIR
References: