A Study to Determine Best Tumor Response With Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2 (HER2) Overexpressing Solid Tumors
Condition: Bladder Cancer; Pancreas Cancer; Cholangiocellular Carcinoma
MeSH terms: Pancreatic Neoplasms; Cholangiocarcinoma
Intervention: Trastuzumab Emtansine
Intervention description: Trastuzumab emtansine will be administered as Regimen A (2.4 mg/kg qw via IV infusion) or Regimen B (3.6 mg/kg q3w via IV infusion) until unacceptable toxicity, withdrawal of consent, disease progression, or death, whichever occurs first.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multicenter, non-randomized, Phase II study will assess the efficacy, safety, and
      pharmacokinetics of trastuzumab emtansine in participants with HER2 overexpressing locally
      advanced (unresectable and not treatable with curative intent) or metastatic urothelial
      bladder cancer (UBC), locally advanced (unresectable and not treatable with curative intent)
      or metastatic pancreatic cancer/cholangiocarcinoma with advanced disease where cure is no
      longer possible and where no other treatment options are available anymore. Participants will
      receive intravenous (IV) infusion of trastuzumab emtansine as Regimen A (2.4 milligrams per
      kilogram [mg/kg], weekly [qw]) or Regimen B (3.6 mg/kg, every 3 weeks [q3w]) until
      unacceptable toxicity, withdrawal of consent, disease progression (PD), or death, whichever
      occurs first. Based on tolerability and safety aspects, steering committee and Independent
      Data Monitoring Committee (iDMC) will decide on expansion of the study to include more
      participants with other carcinoma types.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ in
             greater than or equal to [>/=] 30 percent [%] of tumor cells): locally advanced
             (unresectable and not treatable with curative intent), or metastatic UBC or locally
             advanced (unresectable and not treatable with curative intent) or metastatic
             pancreatic cancer/cholangiocarcinoma

          -  There must be no standard treatment options available for participants with the above
             HER2 overexpressing tumors and they must have undergone at least one prior
             platinum-based treatment for locally advanced (unresectable and not treatable with
             curative intent) or metastatic tumor (Note: for pancreatic cancer/cholangiocarcinoma,
             prior treatments are not required to be platinum-based.)

          -  Participant's lesion should be measurable according to RECIST V1.1 on diagnostic
             computed tomography (CT) scan/magnetic resonance imaging (MRI); Target lesion(s)
             should not have been previously irradiated

          -  At least one formalin-fixed paraffin-embedded (FFPE) biopsy of the primary tumor
             and/or from a metastatic site is required

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2

          -  No significant cardiac history and a current left ventricular ejection fraction (LVEF)
             >/=50%

          -  Adequate organ function

          -  Life expectancy of at least 12 weeks

        Exclusion Criteria:

          -  Participants with previous exposure to HER2-targeted therapies in any setting

          -  Participants showing histologically confirmed focal HER2-expression, that is, less
             than (<) 30% of positively stained tumor cells

          -  Participants with brain metastasis as the sole site of metastatic disease and/or are
             symptomatic or require therapy to control symptoms

          -  Current uncontrolled hypertension (systolic greater than [>] 150 millimeters of
             mercury [mmHg] and/or diastolic >100 mmHg)

          -  Current unstable angina pectoris

          -  History of symptomatic congestive heart failure (CHF) of any New York Heart
             Association (NYHA) criteria or ventricular arrhythmia that requires treatment

          -  History of myocardial infarction within the last 6 months

          -  Peripheral neuropathy, Grade >/=3

          -  Current dyspnea at rest due to complications of advanced malignancy, or other diseases
             that require continuous oxygen therapy

          -  Current severe, uncontrolled systemic disease

          -  History of other malignancy within the last 5 years

          -  Concurrent, serious, uncontrolled infections or current known infection with human
             immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C

          -  Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the
             excipients of the investigational medicinal product (IMP)

          -  Clinically significant bleeding within 30 days before enrollment

          -  Major surgical procedure or significant traumatic injury within 28 days prior to
             randomization or anticipation of the need for major surgery during the course of study
             treatment

          -  Concurrent participation in any other therapeutic clinical trial