treatment protocol of tucatinib with capecitabine and trastuzumab in patients with unresectable previously treated her2+ breast cancer

Conditions: HER2-positive Breast Cancer

Summary: 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).


Eligibility criteria:
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