PHASE I FOLLOWED BY PHASE II STUDY OF THE COMBINATION OF TRASTUZUMAB EMTANSINE (T-DM1) AND CAPECITABINE IN HER2-POSITIVE METASTATIC BREAST CANCER AND HER2-POSITIVE LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER PATIENTS
Inclusion Criteria:
Metastatic Breast Cancer Patients
- ECOG performance status of 0, 1, or 2
- Adequate blood cell count
- Adequate liver, renal and cardiac function
- Histologically or cytologically confirmed breast cancer
- Confirmed HER2-positive disease
- Metastatic breast cancer with at least one measurable lesion according to RECIST
- Disease progression on at least one regimen containing trastuzumab and chemotherapy
- Patients must have recovered from previous treatments
Metastatic Gastric Cancer Patients
- ECOG performance status of 0, 1, or 2
- Adequate blood cell count
- Adequate liver, renal and cardiac function
- Histologically or cytologically confirmed gastric cancer
- HER2-positive tumor (primary tumor or metastatic lesion)
- Inoperable locally advanced or metastatic gastric cancer
Exclusion Criteria:
- Prior treatments before first study treatment:
1. Investigational therapy within = 28 days or 5 half lives, whatever is longest
2. Hormonal therapy within 14 days
3. Trastuzumab within 21 days
- Prior enrollment in a trastuzumab emtansine containing study, regardless of whether
the patient received prior trastuzumab emtansine
- Prior treatment with capecitabine
- History of severe and unexpected reactions to fluoropyrimidine or with known
hypersensitivity to fluorouracil
- Related capecitabine contraindications
- History of intolerance or hypersensitivity to trastuzumab or murine proteins
- History of exposure to cumulative doses of anthracyclines:
- Brain metastases that are symptomatic, or require any radiation, surgery, or steroid
therapy to control their symptoms within 28 days of first study drug administration
- Current peripheral neuropathy of Grade >/= 3 per the NCI CTCAE, v4.0
- History of other malignancy within the last 5 years, except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
or other cancers with a similar outcome as those mentioned above
- Current unstable ventricular arrhythmia requiring treatment
- History of symptomatic congestive heart failure (CHF) (New York Heart Association
[NYHA] Classes II-IV)
- History of myocardial infarction or unstable angina within 6 months prior to first
study drug administration
- History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab
treatment
- Severe dyspnea at rest due to complications of advanced malignancy or requiring
current continuous oxygen therapy
- Clinically significant malabsorption syndrome or inability to take oral medication
- Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease)
- Major surgical procedure or significant traumatic injury within 28 days before
enrollment or anticipation of the need for major surgery during the course of study
treatment
- Current known active infection with HIV, hepatitis B, and/or hepatitis C virus