The purpose of this study is to select targeted treatment based on ex vivo kinase activity inhibition profiles to targeted agents of tumor tissue from patients with advanced cancer for whom no standard treatment is available.

Specific signalling proteins that are important for tumor growth can be targeted by agents. These are called targeted agents or targeted treatment. Thus far, it is unclear which patients will respond to these targeted agents. It is assumed that responses to these agents depend on specific receptor and protein signalling activities in tumor tissues. The investigators propose that kinase activity profiling may be a potential clinical diagnostic tool to predict tumor response to targeted treatment with tyrosine kinase inhibitors.

The investigators will determine ex vivo kinase activity inhibition profiles of tumor tissue to different targeted agents. Tumor tissue from patients with advanced cancer for whom no standard treatment is available will be used.

Patients will be treated with the selected targeted agent and the clinical benefit will be determined.

Inclusion Criteria:

• Patients presenting with an advanced (unresectable and/or metastatic) solid malignancy for whom no standard treatment is available.

• Patients should have received at least one prior standard medical treatment regimen for their advanced disease.

• Patients with progressive disease within 12 weeks prior to the start of study medication based on radiological assessment.

• At least one tumor lesion should be assessable for biopsy to perform kinase activity analysis.

• Age ≥ 18 years.

• Histological or cytological documentation of cancer is required.

• Patients with at least one measurable lesion. Lesions must be evaluated by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST).

• WHO performance status 0 - 2

• Life expectancy of at least 12 weeks

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

  • Hemoglobin ≥ 5.6 mmol/L
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Platelet count ≥ 100x10*9/l
  • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) 22 of 59
  • ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
  • Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ¡Ý 50 ml/min
  • Activated partial thromboplastin time < 1.25 x ULN
  • Prothrombin time or INR < 1.25 x ULN

• Patients should be able to swallow oral medication.

• Written informed consent

Exclusion Criteria:

• History of cardiac disease:

  • Congestive heart failure >NYHA class 2.
  • Active Coronary Artery Disease (myocardial infarction more than 6 months prior to screening is allowed).
  • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).

• Uncontrolled hypertension. Blood pressure must be ≤ 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 3 separate measurements on at least 2 separate days.

• Uncontrolled infections (> grade 2 NCI-CTC version 3.0).

• Subjects with serious non-healing wound, ulcer, or bone fracture.

• History or clinical evidence of central nervous system (CNS) disease, including primary brain tumor and brain metastases.

• Clinical findings associated, in the judgment of the investigator, with an unacceptably high tumor biopsy risk

• Pregnant or breast-feeding subjects.

• Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.

• Radiotherapy on target lesions during study or within 4 weeks of the start of study drug. Palliative radiotherapy will be allowed.

• Concomitant use of dexamethasone, anti-convulsants and anti-arrhythmic drugs other than digoxin or beta blockers.

• Major surgery within 28 days of start of treatment. The surgical wound should be fully healed prior to the start of study drug. In subjects who experienced wound healing complications during therapy, treatment should be withheld until the wound is fully healed.

• Substance abuse, medical, psychological or social conditions that may interfere with the subject¡-s participation in the study or evaluation of the study results.

• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.