Phase 2 Study of Tucatinib vs Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer

Study Purpose

To assess the effect of tucatinib vs.#46; placebo in combination with capecitabine and trastuzumab on progression-free survival (PFS) per RECIST 1.1 based on independent central radiology review.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) methodology Received previous treatment with trastuzumab, pertuzumab, and T-DM1 Progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy Have measurable or non-measurable disease assessable by RECIST 1.1 At least 18 years of age at time of consent Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 Adequate hepatic and renal function Left ventricular ejection fraction (LVEF) ≥ 50% CNS Inclusion

- Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following: - No evidence of brain metastases - Untreated brain metastases not needing immediate local therapy - Previously treated brain metastases not needing immediate local therapy 1.

Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy 2. Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if the following criteria are met: i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days. ii. Other sites of evaluable disease are present c. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions Exclusion Criteria Previously been treated with: 1. lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or toxicity) 2. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) at any time previously 3. previously been treated with capecitabine for metastatic disease except in cases where capecitabine was given for < 21 days and was discontinued for reasons other than disease progression or toxicity. Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible. Clinically significant cardiopulmonary disease Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease Positive for human immunodeficiency virus (HIV) Unable for any reason to undergo MRI of the brain CNS Exclusion

- Based on screening brain MRI, patients must not have any of the following: Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent) Any brain lesion thought to require immediate local therapy.

Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria Known or concurrent leptomeningeal disease (LMD) Poorly controlled seizures

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02614794
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Cascadian Therapeutics Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Luke Walker, MD
Principal Investigator Affiliation	Seattle Genetics, Inc.
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Israel, Italy, Portugal, Spain, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	HER2 Positive Breast Cancer

Additional Details

A randomized, international, multi-center, double-blinded study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. Patients will be randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. Stratification factors include presence or history of treated or untreated brain metastases (yes/no), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs.#46; 1), and region of world (US vs.#46;Canada vs.#46;Rest of World). No crossover from placebo to tucatinib will be allowed. Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Left ventricular ejection fraction will be assessed by MUGA or ECHO at screening and once every 12 weeks thereafter. Contrast brain MRI will be performed at baseline in all patients. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilize RECIST 1.1 and include patients with evaluable tumors defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment is performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain will be required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions are made based upon investigator assessment. All patients undergo a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression. Patients in both arms of the study will be followed for OS after completion of study treatment.

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University of Alabama, Birmingham, Alabama

Status

Recruiting

Address

University of Alabama

Birmingham, Alabama, 35294

Site Contact

Felicia Witherspoon

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