Targeted Therapy Selection Based on Tumor Tissue Kinase Activity Profiles for Patients With Advanced Solid Malignancies, an Exploratory Study
- 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
- 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
- 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
- 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
- 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
- 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.