ACTIVE_NOT_RECRUITING

Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

Conditions

Brain Metastases Human Epidermal Growth Factor 2 Positive Carcinoma of Breast Advanced Breast Cancer HER2+ breast cancer Trastuzumab Pertuzumab T-DM1

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Patients with advanced HER2+ breast cancer on maintenance trastuzumab/pertuzumab or T-DM1 with 1st or 2nd intracranial disease event (brain metastases) and stable extracranial disease will be enrolled. They will receive local therapy with stereotactic radiosurgery ± surgical resection if indicated followed by enrollment. Patients will continue standard of care trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib. Hormone receptor positive patients requiring endocrine therapy should continue. Study treatment will continue until disease progression or intolerable side effects. Patients on trial with extracranial disease progression with stable intracranial disease should continue tucatinib into next line of therapy.

Official Title

Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

Quick Facts

Study Start:2023-03-23

Study Completion:2026-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05323955

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Locally advanced/unresectable or metastatic breast cancer with presence of brain metastases (Stage IV). * Histologically confirmed HER2+ breast carcinoma by ASCO-CAP guidelines, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology on most recent biopsy (primary tissue). * Currently receiving: (1) first-line trastuzumab/pertuzumab with or without endocrine therapy OR (2) second-line T-DM1 in the metastatic setting OR (3) adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence. Patients with de novo metastatic disease and brain metastases or isolated metastatic disease to the brain can enroll at time of initiation of trastuzumab/pertuzumab. Induction taxane therapy is not required and need to administer can be determined by the treating physician. Patients on trastuzumab alone are allowed if pertuzumab not tolerated. * Systemic disease otherwise stable per RECIST 1.1 or no evidence of extracranial disease. * Adequate hepatic and renal function and hematologic parameters: * Absolute neutrophil count (ANC) ≥ 1.0 × 109/L * Platelets ≥ 100 × 109/L * Hemoglobin ≥ 9 g/dL * Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present) * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation * Left ventricular ejection fraction (LVEF) ≥ 50%. * Central nervous system inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have ALL of the following: * Adequate local therapy to existing brain lesions ≥ 5mm including surgical resection and/or stereotactic radiosurgery * Limited to first or second intracranial progression. Third intracranial progression would be considered if \> 12 month interval between second and third intracranial progression. * Time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment. * Time since surgical resection is ≥ 14 days prior to first dose of study treatment. * Time since local therapy \< 12 weeks. Patients with de novo metastastic breast cancer presenting with brain metastases may enter following cessation of chemotherapy if within 24 weeks of local therapy to the brain and brain metastases have remained stable based on brain MRI. * Prior radiation is required within 12 weeks of enrollment to at least 1 brain lesion. Other brain lesions under 5mm do not require treatment. * Females of childbearing potential must have a negative serum pregnancy test at screening. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. * Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.	* Previously been treated with: Lapatinib, neratinib, afatinib, tucatinib or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously (patients treated with adjuvant neratinib allowed if relapse \> 12 months after last dose). * Clinically significant cardiopulmonary disease. * Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including: * tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice), * hepatitis B (known positive HBV surface antigen (HBsAg) result), * hepatitis C, or * human immunodeficiency virus (positive HIV 1/2 antibodies) * Unable for any reason to undergo MRI of the brain * Use of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. See protocol. * Central nervous system exclusion - Based on screening brain MRI, patients must not have any of the following: * Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent) * Diffuse leptomeningeal disease or positive CSF cytology; however, discreet dural-based metastases are allowed * Poorly controlled seizures. Defined as seizures that continue to occur despite optimal anticonvulsant medications based on investigator discretion. * History of whole brain radiation therapy * Any untreated brain lesions ≥ 5 mm * Active infection requiring intravenous systemic therapy. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Patients with a prior or concurrent malignancy within last 3 years whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial. * Treatment with any investigational drug within 30 days prior to registration.

Inclusion Criteria

Exclusion Criteria

* Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Age ≥ 18 years at the time of consent.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
* Locally advanced/unresectable or metastatic breast cancer with presence of brain metastases (Stage IV).
* Histologically confirmed HER2+ breast carcinoma by ASCO-CAP guidelines, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology on most recent biopsy (primary tissue).
* Currently receiving: (1) first-line trastuzumab/pertuzumab with or without endocrine therapy OR (2) second-line T-DM1 in the metastatic setting OR (3) adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence. Patients with de novo metastatic disease and brain metastases or isolated metastatic disease to the brain can enroll at time of initiation of trastuzumab/pertuzumab. Induction taxane therapy is not required and need to administer can be determined by the treating physician. Patients on trastuzumab alone are allowed if pertuzumab not tolerated.
* Systemic disease otherwise stable per RECIST 1.1 or no evidence of extracranial disease.
* Adequate hepatic and renal function and hematologic parameters:
* Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
* Platelets ≥ 100 × 109/L
* Hemoglobin ≥ 9 g/dL
* Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)
* Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation
* Left ventricular ejection fraction (LVEF) ≥ 50%.
* Central nervous system inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have ALL of the following:
* Adequate local therapy to existing brain lesions ≥ 5mm including surgical resection and/or stereotactic radiosurgery
* Limited to first or second intracranial progression. Third intracranial progression would be considered if \> 12 month interval between second and third intracranial progression.
* Time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment.
* Time since surgical resection is ≥ 14 days prior to first dose of study treatment.
* Time since local therapy \< 12 weeks. Patients with de novo metastastic breast cancer presenting with brain metastases may enter following cessation of chemotherapy if within 24 weeks of local therapy to the brain and brain metastases have remained stable based on brain MRI.
* Prior radiation is required within 12 weeks of enrollment to at least 1 brain lesion. Other brain lesions under 5mm do not require treatment.
* Females of childbearing potential must have a negative serum pregnancy test at screening. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
* Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.

* Previously been treated with: Lapatinib, neratinib, afatinib, tucatinib or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously (patients treated with adjuvant neratinib allowed if relapse \> 12 months after last dose).
* Clinically significant cardiopulmonary disease.
* Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
* tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice),
* hepatitis B (known positive HBV surface antigen (HBsAg) result),
* hepatitis C, or
* human immunodeficiency virus (positive HIV 1/2 antibodies)
* Unable for any reason to undergo MRI of the brain
* Use of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. See protocol.
* Central nervous system exclusion - Based on screening brain MRI, patients must not have any of the following:
* Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)
* Diffuse leptomeningeal disease or positive CSF cytology; however, discreet dural-based metastases are allowed
* Poorly controlled seizures. Defined as seizures that continue to occur despite optimal anticonvulsant medications based on investigator discretion.
* History of whole brain radiation therapy
* Any untreated brain lesions ≥ 5 mm
* Active infection requiring intravenous systemic therapy.
* Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
* Patients with a prior or concurrent malignancy within last 3 years whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
* Treatment with any investigational drug within 30 days prior to registration.

Contacts and Locations

Principal Investigator

Carey Anders, MD

PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Study Locations (Sites)

University of California San Francisco

San Francisco, California, 94158

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Michigan Health System

Ann Arbor, Michigan, 48109

United States

Washington University in St. Louis

Saint Louis, Missouri, 63130

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Providence Portland Medical Center

Portland, Oregon, 97213

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Carey Anders, M.D.

Carey Anders, MD, PRINCIPAL_INVESTIGATOR, Duke Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-23

Study Completion Date2026-07

Study Record Updates

Study Start Date2023-03-23

Study Completion Date2026-07

Terms related to this study

Keywords Provided by Researchers

Brain metastases
HER2+ breast cancer
Trastuzumab
Pertuzumab
T-DM1

Additional Relevant MeSH Terms

Brain Metastases
Human Epidermal Growth Factor 2 Positive Carcinoma of Breast
Advanced Breast Cancer