Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Breast: Metastatic
NCT ID: NCT02154529 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 14-231

 

Evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of the combination of KD019 and trastuzumab in subjects with HER2-positive metastatic breast cancer

 

Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:
Nancy Lin, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:
Dana-Farber Cancer Institute: Breast Cancer Nursing Team, 617-632-3478

Eligibility Criteria

Inclusion Criteria: - Females with histologically or cytologically confirmed HER2-positive breast cancer. HER2-positive is defined as 3+ staining by immunohistochemistry, or HER2 gene amplification by fluorescent in situ hybridization or silver in situ hybridization with HER2/CEP17 ratio ≥ 2.0 with average HER2 copy number ≥ 4.0 signals/cell - Metastatic disease that has progressed on previous therapy - Subjects may have received any number of prior therapies for breast cancer: - Previous therapies must have included trastuzumab, pertuzumab, and trastuzumab emtansine. However, subjects starting initial systemic therapy for HER2-positive breast cancer prior to June 2012, when pertuzumab was approved for initial treatment of patients with HER2-positive breast cancer, are not required to have had pertuzumab - If the subject has ER+ breast cancer, prior therapy must have included at least 1 hormonal therapy - Subjects with brain metastases must have received radiation therapy prior to study entry - Subjects with disease progression in the brain after prior brain radiation therapy may have extra CNS metastases in any location or may have no extra CNS metastases - Enrollment in the expansion Phase 2a portion of the study will be limited to subjects with HER2-positive metastatic breast cancer with brain metastases that have progressed after radiation therapy - At least 1 measurable and new or progressing breast cancer lesion that is ≥ 10mm by spiral CT scan or by brain MRI - No increase in corticosteroid dose during the week prior to screening brain MRI - No history of another malignancy in the past 5 years, except treated non-melanoma skin cancer or superficial bladder cancer or carcinoma-in-situ of the cervix - Adequate organ and bone marrow functions - Serum potassium and magnesium levels within normal limits - Cardiac injection fraction ranging from 55% or 70% as measure by echocardiogram - No coexisting medical problems of sufficient severity to limit compliance with the study - Women of childbearing potential must have negative urine pregnancy test. They must agree to use highly effective method of birth control during the study and for 3 months after the termination of the study. Highly effective birth control methods include implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomized partner Exclusion Criteria: - Any concurrent therapy for breast cancer other than the specified treatment in this study. Concurrent treatment will biphosphonates is allowed - Cerebrospinal fluid cytology positive for malignant cells or symptomatic leptomeningeal carcinomatosis - Taking any medication known to inhibit the CYP3A4 isozyme or any drugs that are CYP3A4 inducers (including phenytoin), or any drugs associated with torsades de pointes or known to prolong the QTc(f) interval, including anti-arrhythmic medications within 2 weeks prior to Day 1 of treatment on study. A stable regimen of antidepressants of the SSRI class is allowed - Has evidence of active heart disease within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction - History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block, or congenital long QT syndrome. Subjects with a history of atrial arrhythmias should be discussed with the medical monitor - Has an active infectious process - Subject who is pregnant or lactating - Known contraindications to MRI, such as cardiac pacemaker, shrapnel, or ocular foreign body - Had had major surgery without fully recovery - Has marked prolongation of QTc interval at screening or baseline using the Fridericia method of correction for heart rate - Has gastrointestinal tract disease resulting in an inability to take or absorb oral medication
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