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

HER2-positive Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Approved for marketing

Administrative data

• NCT number: NCT04220203
• Other study ID #: SGNTUC-021
• Status: Approved for marketing

Study information

• Verified date: May 2020
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial 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).

Recruitment information / eligibility

• Status: Approved for marketing
• Enrollment: 0
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.	Parexel