Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens.

HER2-positive Breast Cancer Clinical Trial

— TRACE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05253911
• Other study ID #: IOM-120465
• Status: Recruiting
• Start date: May 21, 2022
• Est. completion date: May 2027

Study information

• Verified date: April 2024
• Source: iOMEDICO AG
• Contact: Cathrin Hogrefe, Dr.
• Phone: +49761152420
• Email: Trace[@]iomedico.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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,

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• TUKYSA®
tucatinib/trastuzumab/capecitabine according to TUKYSA® SmPC.

Locations

Country	Name	City	State
Austria	Medizinische Universität Wien, Innere Medizin I, Hämatologie und Onkologie	Vienna
Germany	Universitätsklinikum Essen, Innere Klinik (Tumorforschung)	Essen	Northrhine-Westphalia

Sponsors (2)

Lead Sponsor	Collaborator
iOMEDICO AG	Seagen Inc.

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of planned hospitalizations	Number of planned hospitalizations will be measured using descriptive statistics.	Baseline, up to 5 years
Other	Duration of planned hospitalizations	Duration of planned hospitalizations will be measured using descriptive statistics.	Baseline, up to 5 years
Other	Duration of sick leaves	Duration of sick leaves will be measured using descriptive statistics.	Baseline, up to 5 years
Primary	Time to deterioration of EORTC global health scale by at least 10 points	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
Primary	Changes in the global health scale	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	Time to next systemic treatment (TTNT)	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
Secondary	Time to local intracranial treatment (TLT)	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
Secondary	Overall survival (OS)	OS is defined as time from first administration of any study treatment to death from any cause.	Baseline, up to 5 years
Secondary	Overall response rate (ORR)	ORR is defined as proportion of patients with any response (partial or complete remission) overall.	Baseline, up to 5 years
Secondary	Duration of response (DOR)	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
Secondary	Clinical benefit rate (CBR)	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
Secondary	Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE	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
Secondary	Safety laboratory value: Aspartate aminotransferase (AST)	During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of AST (Aspartate aminotransferase) measured will be documented continously during tucatinib treatment. Baseline levels of AST will be presented using descriptive statistics.	Baseline, up to 30 days after end of tucatinib treatment
Secondary	Safety laboratory value: Alanine aminotransferase (ALT)	During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of ALT (Alanine aminotransferase) measured will be documented continously during tucatinib treatment. Baseline levels of ALT will be presented using descriptive statistics.	Baseline, up to 30 days after end of tucatinib treatment
Secondary	Safety laboratory value: bilirubin	During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of bilirubin measured will be documented continously during tucatinib treatment. Baseline levels of bilirubin will be presented using descriptive statistics.	Baseline, up to 30 days after end of tucatinib treatment
Secondary	Therapy decision making	Frequencies and percentages of parameters affecting therapy choice.	Baseline
Secondary	Previous antineoplastic Therapies	Frequency/type of previous systemic antineoplastic treatments (neoadjuvant/adjuvant/palliative)	Baseline
Secondary	Previous anti-HER2 regimens	Frequency and type of previous anti-HER2 based regimens	Baseline
Secondary	Subsequent antineoplastic therapies	Frequency and type of subsequent systemic antineoplastic therapies	End of treatment, up to 5 years
Secondary	Local antineoplastic therapies	Frequency and type of local antineoplastic therapies (surgeries, radiotherapies) incl. local intracranial therapies	Baseline, up to 5 years
Secondary	Details on line of treatment for both cohorts	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
Secondary	Treatment Duration	Treatment duration of study treatment in total and per substance	Baseline, up to 5 years
Secondary	Dose intensity	Dose intensity (absolute and relative) for each substance as prescribed by the treating physician	Baseline, up to 5 years
Secondary	Dose modifications	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
Secondary	Therapy management (use of relevant supportive medications)	Frequency of usage of antidiarrheal drugs for prophylaxis and treatment of tucatinib-induced diarrhea	Baseline, up to 5 years