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

NCT05323955 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Pro00109777
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

Brain metastases; HER2+ breast cancer; Trastuzumab; Pertuzumab; T-DM1

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Evaluate the ability of tucatinib in combination with trastuzumab/pertuzumab or TDM-1 to prolong intracranial progression free survival (PFS) in patients compared to historical controls. PFS is defined as the time from the day of study treatment initiation until evidence of intracranial disease progression per RANO-BM or death from any cause.

  3 years

Secondary Outcomes (6)

• Progression Free Survival by RECIST 1.1

  3 years

• Progression Free Survival of Extracranial Disease

  3 years

• Distant Versus Local Intracranial Progression Free Survival

  3 years

• Site of First Progression

  3 years

• Overall Survival (OS)

  3 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Trastuzumab/pertuzumab + tucatinib or T-DM1 + tucatinib 300mg of tucatinib taken orally twice a day. Taken on Days 1-21 of a 21 Day cycle (3 Weeks). Trastuzumab/Biosimilar administered per current package insert based on site standard of care guidelines Pertuzumab or Biosimilar administered per current package insert based on site standard of care guidelines Trastuzumab Emtansine (T-DM1) administered per current package insert based on site standard of care guidelines

Drug: Trastuzumab; Drug: Trastuzumab Emtansine (T-DM1); Drug: Pertuzumab; Drug: Tucatinib

Interventions

Trastuzumab DRUG

Administer per current package insert based on site standard of care guidelines

Also known as: Herceptin

Experimental Group

Tucatinib DRUG

300 mg orally twice daily (21 Day Cycle)

Also known as: Tukysa

Experimental Group

Trastuzumab Emtansine (T-DM1) DRUG

Administer per current package insert based on site standard of care guidelines

Experimental Group

Pertuzumab DRUG

Administer per current package insert based on site standard of care guidelines

Also known as: Perjeta

Experimental Group

Eligibility Criteria

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

You may qualify if:

• 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%.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• 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)
• NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy. Testing not required.
• 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.
• 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

Sponsors & Collaborators

• Pfizer: collaborator
• Carey Anders, M.D.: lead

Study Sites (8)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Trastuzumab; Ado-Trastuzumab Emtansine; pertuzumab; tucatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Carey Anders, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 12, 2022
• Study Start: March 23, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)