Treatment Protocol of Tucatinib With Capecitabine and Trastuzumab in Patients With Unresectable Previously Treated HER2+ Breast Cancer

Study Overview
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Brief Summary
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The purpose of this program is to provide access to tucatinib in the United States before FDA approval. Participants will receive a combination treatment of capecitabine, trastuzumab, and tucatinib. All treatments will be given on a 21 day cycle. To learn more about this program, contact Seattle Genetics' Medical Information (medinfo@seagen.com).

Official Title
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A Multicenter, Open-label, Treatment Protocol of Tucatinib in Combination With Capecitabine and Trastuzumab in Patients With Previously Treated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: Tucatinib
* Drug: Capecitabine
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by ISH or FISH or IHC methodology For patients WITHOUT presence or history of brain metastases, have received previous treatment with trastuzumab, pertuzumab, and T-DM1 For patients WITH presence or history of brain metastases, have received previous treatment with trastuzumab Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by treating physician), or be intolerant of last systemic therapy Have measurable disease or non-measurable disease assessable by standard of care imaging methods Have ECOG PS 0 or 1 Have a life expectancy of at least 6 months, in the opinion of the treating physician Exclusion Criteria: Eligible for a tucatinib clinical trial Disease recurrence within 3 months of last capecitabine for metastatic disease History of allergic reactions to trastuzumab, capecitabine, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed, or known allergy to one of the excipients in the protocol drugs Have received treatment with any systemic anti-cancer therapy (excluding hormonal therapy), non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of protocol treatment or are currently participating in an interventional clinical trial. Have received hormonal therapies <1 week of the first dose of protocol treatment. Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions: Alopecia and neuropathy, which must have resolved to ≤ Grade 2 CHF, which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely Anemia, which must have resolved to ≤ Grade 2 Have clinically significant cardiopulmonary disease Have known myocardial infarction or unstable angina within 6 months prior to first dose of protocol treatment Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease with uncontrolled disease Are known to be positive for HIV with uncontrolled disease Are pregnant, breastfeeding, or planning a pregnancy Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed) Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a CYP2C8 or CYP3A4 inducer within 5 day prior to start of tucatinib treatment. Have known dihydropyrimidine dehydrogenase deficiency Have evidence within 2 years of the start of protocol treatment of another malignancy that required systemic treatment. CNS Exclusion - patients must not have any of the following: Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor and approval for enrollment is given Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, patients on a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by the medical monitor Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g. brain stem lesions). Known or suspected LMD as documented by the treating physician Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tucatinib|300 mg orally two times per day|
|Drug: Capecitabine|1000 mg/m^2 orally two times per day on Days 1-14 of each 21-day cycle|
|Drug: Trastuzumab|Loading dose of 8 mg/kg into the vein (IV; intravenously), followed by 6 mg/kg IV once per 21-day cycle|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |