MSC2015103B in Solid Tumors
Condition: Advanced Solid Tumor
MeSH terms: Neoplasms
Intervention: MSC2015103B; MSC2015103B
Intervention description: Schedule 1: MSC2015103B will be administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD establishment. Starting dose will be 150 microgram (mcg), which will be escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.; Schedule 2: MSC2015103B will be administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose will be 150 mcg, and will be escalated to 200 mcg subsequently.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MEK inhibitor; Solid Tumor; Phase I

Summary:

      The main purpose of this study is to test the experimental drug, MSC2015103B at different
      dose levels and on different treatment schedules, to see whether it is safe and can be
      tolerated when given to subjects once a day one day per week over a 21-day period or once a
      day three times per week over a 21-day period. The investigators would also like to find out
      how MSC2015103B is broken down by the body.

      Additional purposes of the trial are to assess side effects of MSC2015103B and to find out
      whether MSC2015103B has anti-cancer effects. In addition, the investigators would like to
      explore pharmacokinetics.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed solid tumor preferably, but not exclusively, including
             pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast,
             ovarian carcinoma, or melanoma which is locally advanced or metastatic, and either
             refractory after standard therapy for the disease or for which no effective standard
             therapy is available

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal
             to (<=) 1

          -  Has read and understands the informed consent form and is willing and able to give
             informed consent. Fully understands requirements of and willing to comply with all
             trial visits and assessments

          -  Evidence of measurable disease at trial entry as per Response Evaluation Criteria In
             Solid Tumors (RECIST) v1.0.

          -  Willing to provide archival tissue samples for molecular analysis

        Other inclusion criteria as defined in protocol.

        Exclusion Criteria

          -  Bone marrow impairment as evidenced by hemoglobin less than (<) 9.0 gram per deciliter
             (g/dL), neutrophil count < 1.5 x 10^9 per liter (/L), and/or platelets <100 x 10^9/L
             per liter (/L)

          -  Renal impairment as evidenced by serum creatinine greater than (>) 1.5 x upper limit
             of normal (ULN) and/or calculated creatinine clearance < 50 milliliter per minute
             (mL/min) (Cockcroft-Gault formula)

          -  Liver function and liver cell integrity abnormality as defined by total bilirubin >
             1.5 x ULN, or aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 2.5 x
             ULN, for subjects with liver involvement AST/ALT > 5 x ULN. Subjects with albumin <
             2.5 g/dL are also excluded

          -  History of central nervous system (CNS) metastases.

          -  History of difficulty of swallowing, malabsorption, or other chronic gastrointestinal
             disease or conditions that may hamper compliance and/or absorption of the tested
             product.

          -  Chronic diarrhea that is >= Grade 2 in severity

          -  Clinically significant cardiac conduction abnormalities

          -  A left ventricular ejection fraction of < 45%

          -  A history of stroke or myocardial infarction within the past year

          -  A history of uveitis and scleritis

          -  Retinal pathology beyond normal age-related processes

          -  Evidence of a retinal vein occlusion on fluorescein angiogram or a history of retinal
             vein occlusion

          -  Subjects are also excluded if their ophthalmologist finds that their optic disc is at
             risk for a central retinal vein occlusion

          -  History of glaucoma

          -  Subjects requiring daily and/or chronic systemic steroids

          -  Pregnant or nursing females Other exclusion criteria as defined in protocol.