NCT05583110

Efficacy and Safety of the Combination of Trastuzumab Plus TUCAtinib Plus viNorelbine in Patients With HER2-positive Non-resectable Locally Advanced or Metastatic Breast Cancer

Single Arm Phase II Study of the Efficacy and Safety of the Combination of Trastuzumab Plus TUCAtinib Plus viNorelbine in Patients With HER2-positive Non-resectable Locally Advanced or Metastatic Breast Cancer "TrasTUCAN Study"

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Spanish Breast Cancer Research Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Breast cancer (BC) is the most common neoplasm in the world. In Spain, one in 8 women is diagnosed with BC. The human epidermal growth factor receptor 2 (HER2)-positive BC subtype (that represents around 20% of all BC) was associated with poor prognosis however, new therapeutic advances have significantly increased the cure rate of patients in early stages. In the metastatic setting, anti-HER2 targeted therapies have significantly improved overall survival (OS) with good quality of life, however there is still a substantial group of patients who die, and therefore additional drugs need to be investigated. Trastuzumab, an anti HER2 antibody has demonstrated, in combination with chemotherapy, an improvement of OS in early and metastatic stages. Tucatinib is an oral selective inhibitor of the HER2 receptor tyrosine kinase subunit. Its high affinity for this subunit causes fewer toxicities, such as rash and diarrhea, which are common with other anti-HER tyrosine kinase inhibitors (TKIs). Vinorelbine has been evaluated previously in combination with trastuzumab showing interesting results. This is a single country, multicenter, single arm phase II clinical trial with a safety run-in phase, to study the efficacy, safety and tolerability of the administration of tucatinib in combination with trastuzumab and vinorelbine in HER2-positive non-resectable locally advanced or metastatic breast cancer (MBC) with measurable disease.

Detailed description

Patients with brain metastasis are allowed (but up to maximum of 50% of included patients). Forty-nine patients will be enrolled in the study: * The first 3 patients included in the study will receive trastuzumab plus tucatinib plus oral vinorelbine at a dose of 50 mg/m2 in the first cycle. If not dose limiting toxicity (DLT) is observed, these patients will receive oral vinorelbine at a dose of 60 mg/m2 for the following cycles. * If 1/3 patients experience DLT in the first cycle, 3 additional patients will be included to receive trastuzumab plus tucatinib plus oral vinorelbine at a dose of 50 mg/m2 in the first cycle and then 60 mg/m2. * If 0/3 or \<2/6 patients experience DLT in the first cycle the vinorelbine dose will be 60 mg/m2 for all the following patients included in the study. * If ≥2 out of 3 or 6 patients experienced DLT in the first cycle, all the following included patients will receive oral vinorelbine at a dose of 50 mg/m2. DLTs are defined according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as any of the following events considered by the investigator to be related to investigational treatment: * Grade 4 neutropenia lasting more than 7 consecutive days or associated with fever. * Grade 4 thrombocytopenia lasting more than 7 consecutive days. * Grade 3 thrombocytopenia associated with clinically significant bleeding. * Platelet count \<10,000/mm3. * Delay of more than 7 days in the initiation of a subsequent cycle due to treatment-related adverse events. * Any grade 3 or higher non-hematologic toxicity (except grade 3 or higher nausea/emesis or diarrhea in the absence of optimal symptomatic treatment for these conditions, grade 3 or higher fatigue lasting less than 1 week and other grade 3 or higher non-hematologic toxicity that could be controlled to grade 2 or less with appropriate treatment). Justification of Sample size determination: The A'Hern one stage design will be used for this study. Taking into account the HERCLIMB study, we assume a null hypothesis (H0) of an Objective response rate (ORR) of 23% and alternative hypothesis (H1) of an ORR of 40%. With an alpha error of 0.05 and a statistical power of 80%, we will need to include 46 evaluable patients. Assuming a 5% dropout rate, 49 patients will be included in this study. Patients included in the run-in phase will be considered for the efficacy analysis of the phase II. Study Duration: The start date of the study is the date of the first site activation. Recruitment period will occur during approximately 18 months from the first patient in. The end date of the study is the date of the last visit of the last patient (LPLV), including follow-up. The duration of the study will be approximately 40 months from the first patient in. Performing exploratory objectives will be independent of the date of the end of the study.

Conditions

• HER2-positive Metastatic Breast Cancer
• Locally Advanced HER2 Positive Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Tucatinib	Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.
DRUG	Trastuzumab	Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.
DRUG	Vinorelbine	Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.

Timeline

• Start date: 2023-03-08
• Primary completion: 2025-05-30
• Completion: 2025-05-30
• First posted: 2022-10-17
• Last updated: 2025-12-10

Locations

18 sites across 1 country: Spain