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

NCT05583110 | Terminated Phase 2

• 2 other identifiers: GEICAM/2020-082021-002561-18
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

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

Keywords

tucatinib; Non-resectable locally advanced or metastatic breast cancer; HER2-positive

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate (ORR) defined as the rate of complete response (CR) plus partial response (PR) based on the investigator's assessment using the response evaluation criteria for solid tumors (RECIST) version 1.1., out of the patients who received at least 1 dose of treatment.

  Approximately 26 months from the inclusion of the first patient

Secondary Outcomes (9)

• ORR in patients with brain metastasis at baseline

  Approximately 26 months from the inclusion of the first patient

• Progression-free survival (PFS)

  Approximately 26 months from the inclusion of the first patient

• Duration of response (DOR)

  Approximately 26 months from the inclusion of the first patient

• Disease control rate (DCR)

  Approximately 26 months from the inclusion of the first patient

• Clinical benefit rate (CBR)

  Approximately 26 months from the inclusion of the first patient

Study Arms (1)

Trastuzumab-Vinorelbine-Tucatinib

EXPERIMENTAL

Trastuzumab-Vinorelbine-Tucatinib

Drug: Tucatinib; Drug: Trastuzumab; Drug: Vinorelbine

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.

Also known as: Tukysa

Trastuzumab-Vinorelbine-Tucatinib

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.

Also known as: Herceptin

Trastuzumab-Vinorelbine-Tucatinib

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.

Also known as: Navelbine

Trastuzumab-Vinorelbine-Tucatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible to be enrolled in the study only if they meet all of the following criteria:
• Written and signed informed consent obtained prior to any study-specific procedure.
• Male or female patients at least 18 years of age.
• Availability of pre-treatment archival Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue (preferably the most recent available), otherwise possibility to perform a biopsy, to carry out exploratory biomarker analyses.
• Documented HER2-positive status by local laboratory determination, preferably on the most recent available FFPE tumor sample, according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay.
• Previous therapy with at least two prior anti-HER2 treatment regimens (either in early stage or advanced disease). Prior taxanes and trastuzumab are mandatory. Prior treatment with pertuzumab, T-DM1, trastuzumab-deruxtecan and anti-HER2 TKI agents is allowed.
• Measurable disease according to RECIST 1.1 criteria, defined as at least 1 extra-osseous lesion that can be accurately measured in at least 1 dimension.
• Mandatory contrast brain magnetic resonance imaging (MRI) must be performed at baseline and patients must have at least one of the following:
• No evidence of brain metastases.
• Untreated brain metastases not needing immediate local therapy.
• Previously treated brain metastases.
• Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local central nervous system (CNS) therapy, provided that there is no clinical indication for immediate re-treatment with local therapy.
• Subjects treated with CNS local therapy for newly identified lesions may be eligible to enroll if all of the following criteria are met:
• Time since stereotactic radiosurgery (SRS) is at least 1 week prior to first dose of study treatment, time since whole brain radiation therapy (WBRT) is at least 3 weeks prior to first dose, or time since surgical resection is at least 4 weeks.
• Other sites of evaluable disease are present.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Have received more than 4 lines of systemic therapy for locally advanced or MBC.
• Have received prior treatment with tucatinib, vinorelbine for locally advanced or MBC or anti-HER2 TKI agents if administered less than 12 months prior to study entry.
• Have used a strong CYP3A4 or CYP2C8 inhibitor or CYP3A substrate within 2 weeks, or a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment (see Protocol Attachment 2 for more information).
• Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed).
• Any investigational agent within 4 weeks.
• Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. \< 3 weeks for fluorouracil, doxorubicine, epirubicin or \< 1 week for weekly chemotherapy).
• Biologic therapy (e.g., antibodies): up to 4 weeks prior to starting study treatment.
• Endocrine therapy: tamoxifen or aromatase inhibitor (AI) within 2 weeks prior to starting study treatment.
• Corticosteroids within 2 weeks prior to starting study treatment. Note: the following uses of corticosteroids are permitted at any time: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
• Radiotherapy within 2 weeks (3 weeks if WBRT) prior to starting study treatment (all acute toxic effects must be resolved to NCI-CTCAE version 5.0 grade \<1, except toxicities not considered a safety risk for the patient at investigator´s discretion). Patients who received prior radiotherapy to \>25% of bone marrow are not eligible regardless of when it was administered.
• Major surgery or other anti-cancer therapy not previously specified within 4 weeks prior to starting study treatment, Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion) is mandatory.
• Are unable for any reason to undergo MRI of the brain.
• Have any of the following with regards to CNS disease:
• Any untreated brain lesions \>2 cm in size.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Seagen Inc.: collaborator

Study Sites (18)

Hospital Universitario de Jeréz De La Frontera

Cadiz, Andalusia, 11407, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Andalusia, 14004, Spain

Location

Hospital Universitario de Jaén

Jaén, Andalusia, 23007, Spain

Location

Hospital Costa del Sol

Málaga, Andalusia, 29603, Spain

Location

Hospital Universitario Virgen de Valme

Seville, Andalusia, 41014, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Hospital Nuestra Señora de Sonsoles

Ávila, Castille and León, 05004, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Castille and León, 47003, Spain

Location

ICO Badalona

Barcelona, Catalonia, 08916, Spain

Location

Hospital Universitario de Bádajoz

Bádajoz, Extremadura, 06080, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Galicia, 36213, Spain

Location

Complejo hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, Las Palmas, 35016, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital San Juan de Alicante

Alicante, Valencia, 03550, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28009, Spain

Location

Hospital Universitario Quironsalud Madrid

Madrid, 28223, Spain

Location

Hospital Universitario de Araba

Vitoria-Gasteiz, Álava, 01009, Spain

Location

Related Links

• GEICAM is a Spanish Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; Trastuzumab; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Study Director

  Hospital General Universitario Gregorio Marañón, Madrid, Spain

  STUDY DIRECTOR

• Study Director

  Hospital Universitario Donostia, San Sebastián, Spain.

  STUDY DIRECTOR

• Study Director

  Hospital Universitario Reina Sofía, Córdoba, Spain

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 17, 2022
• Study Start: March 8, 2023
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (18)