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

Sponsor
Spanish Breast Cancer Research Group
Study ID
NCT05583110
Phase
PHASE2
Status
Terminated

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tucatinib — DRUG
    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.
  • Trastuzumab — DRUG
    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.
  • Vinorelbine — DRUG
    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.

Study Details

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.

Key Dates

Start date
Mar 8, 2023
Status verified
Dec 2025
Primary completion
May 30, 2025
Completion
May 30, 2025

Study Design

Enrollment
13 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Trastuzumab-Vinorelbine-Tucatinib
    Trastuzumab-Vinorelbine-Tucatinib

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Approximately 26 months from the inclusion of the first patient ]

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