A Combination Study of Kadcyla (Trastuzumab Emtansine) and Capecitabine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (mBC) or HER2-Positive Locally Advanced/Metastatic Gastric Cancer (LA/mGC)
Condition: Breast Cancer; Gastric Cancer
MeSH terms: Breast Neoplasms; Stomach Neoplasms
Intervention: Capecitabine; Trastuzumab emtansine (T-DM1); Trastuzumab emtansine (T-DM1); Capecitabine
Intervention description: Capecitabine will be administered at de-escalating doses (starting from 750 mg/m^2) to determine the MTD.; Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg via IV infusion every 3 weeks.; Trastuzumab emtansine will be administered at a dose of 2.4 mg/kg via IV infusion every week.; Capecitabine will be administered at the MTD determined in Cohort 1.
Intervention MeSH terms: Capecitabine; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 182.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multicenter study will assess the maximum tolerated dose (MTD) of capecitabine in
      combination with Kadcyla (trastuzumab emtansine) in participants with HER2-positive mBC or
      HER2-positive LA/mGC using a Phase 1 design, followed by a randomized, open-label Phase 2
      part to explore the efficacy and safety of the combination of Kadcyla and capecitabine
      compared with Kadcyla alone in participants with mBC. The anticipated time on study treatment
      is until disease progression, intolerable toxicity, withdrawal of consent, or study end.
    

Eligibility criteria:

        Inclusion Criteria:

        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

        Exclusion Criteria:

        Metastatic Breast Cancer

          -  Prior treatments before first study treatment:

               1. Investigational therapy within 28 days or 5 half-lives, whichever is longer

               2. Hormonal therapy within 14 days

               3. 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

               1. Treatment with sorivudine or chemically-related analogues

               2. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or
                  glucose-galactose malabsorption

               3. 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)