Resumen

Este ensayo clínico multicéntrico evaluará la dosis máxima tolerada (DMT) de capecitabina en combinación con Kadcyla (trastuzumab emtansina) en participantes con cáncer de mama metastásico (CMm) HER2 positivo o cáncer gástrico localmente avanzado/metastásico (CG-LA/m) HER2 positivo mediante un diseño de Fase 1, seguido de una Fase 2 aleatorizada y abierta para explorar la eficacia y la seguridad de la combinación de Kadcyla y capecitabina en comparación con Kadcyla solo en participantes con CMm. El tiempo previsto de tratamiento en el ensayo es hasta la progresión de la enfermedad, toxicidad intolerable, retirada del consentimiento o finalización del estudio.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Metastatic Breast Cancer
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Adequate blood cell count
Adequate liver, renal, and cardiac function
Life expectancy greater than or equal to (\>/=) 12 weeks
Histologically or cytologically confirmed breast cancer
Confirmed HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or in situ hybridization (ISH)-positive
mBC with at least one measurable lesion according to RECIST v1.1
Disease progression on at least one prior regimen containing trastuzumab and chemotherapy either separately or in combination; participants may be eligible to receive study therapy in first-line setting if trastuzumab and chemotherapy were given in the neoadjuvant/adjuvant setting
Participant must have recovered from previous treatments
Locally Advanced/Metastatic Gastric Cancer
ECOG performance status of 0, 1, or 2
Adequate blood cell count
Adequate liver, renal, and cardiac function
Life expectancy \>/= 12 weeks
Histologically or cytologically confirmed LA/mGC
HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or IHC 2+ and ISH-positive
Inoperable LA/mGC

Criterios de exclusión

Metastatic Breast Cancer
Prior treatments before first study treatment:
Investigational therapy within 28 days or 5 half-lives, whichever is longer
Hormonal therapy within 14 days
Trastuzumab within 21 days
Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received trastuzumab emtansine
Prior treatment with capecitabine
History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil
Related capecitabine contraindications
Treatment with sorivudine or chemically-related analogues
Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
Complete absence of dihydropyrimidine dehydrogenase (DPD) activity
History of intolerance or hypersensitivity to trastuzumab or murine proteins or any product component
History of exposure to high cumulative doses of anthracyclines
Brain metastases that are symptomatic or require radiation, surgery, or steroid therapy to control symptoms within 28 days before study drug
Current peripheral neuropathy of Grade \>/=3
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
Current unstable ventricular arrhythmia requiring treatment
History of symptomatic congestive heart failure (CHF)
History of myocardial infarction or unstable angina within 6 months prior to study drug
History of left ventricular ejection fraction (LVEF) less than (\<) 40% or symptomatic CHF with previous trastuzumab treatment
Severe dyspnea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy
Clinically significant malabsorption syndrome or inability to take oral medication
Current severe, uncontrolled systemic disease (such as 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 study treatment
Current known active infection with human immunodeficiency virus (HIV) or hepatitis B or C
Lapatinib within 14 days before study drug
Locally Advanced/Metastatic Gastric Cancer
Same as above, with addition of previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrollment into the study)

Intervenciones

drug

Capecitabine

Capecitabine will be administered at de-escalating doses (starting from 750 mg/m\^2) to determine the MTD.

drug

Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.

drug

Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.

drug

Capecitabine

Capecitabine will be administered at the MTD determined in Cohort 1.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Capecitabine

Trastuzumab emtansine (T-DM1)

Trastuzumab emtansine (T-DM1)

Capecitabine

Ubicaciones

Fundacion Investigar

Centro Oncologico Riojano Integral (CORI)

Patrocinadores