An Dose Escalation Study of Treatment With BIBF 1120 in Patients With Advanced Solid Tumours

A Phase I Open Label Dose Escalation Study of Continuous Once-daily or Twice Daily Oral Treatment With BIBF 1120 in Patients With Advanced Solid Tumours

Maximum Tolerated Dose (MTD), safety, pharmacokinetics, efficacy of BIBF 1120, pharmacodynamic parameters (Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI))

Inclusion Criteria:

• Male or female patients with confirmed diagnosis of advanced, non resectable and/or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who were not amenable to established forms of treatment
• Measurable tumour deposits by one or more techniques (X-ray), Computed Tomography (CT), Magnetic Resonance Imaging (MRI))
• At least one tumour lesion considered suitable for DCE-MRI as determined by discussion with centre radiologist. This lesion must not have been previously irradiated
• Age 18 years or older
• Life expectancy of at least three months
• Written informed consent given consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
• Patients completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies

Exclusion Criteria:

• Surgical procedures within four weeks of initiating treatment with the study drug, active ulcers, or injuries with incomplete wound healing
• Active infectious disease
• Uncontrolled, severe hypertension (diastolic BP (Blood Pressure) >100 mmHg, Systolic BP>180 mmHg)
• Gastrointestinal disorders that might have interfered with the resorption of the study drug
• Serious illness or concomitant non-oncological disease considered by the investigator to have been incompatible with the protocol
• Brain metastases requiring therapy
• Absolute neutrophil count less than 1500/mm3
• Platelet count less than 100 000/mm3
• Bilirubin greater than 1.5 mg/dl (>26 μmol/L, System International (SI) unit equivalent)
• Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
• Serum creatinine greater than 1.5 mg/dl (>132μmol/L, SI unit equivalent)
• Women and men who were sexually active and unwilling to use a medically acceptable method of contraception
• Pregnancy or breastfeeding
• Treatment with other investigational drugs; chemotherapy or hormone therapy (excluding Lutenizing Hormone Releasing Hormone (LHRH) agonists or bisphosphonates provided the lesion for MR (magnetic resonance) imaging did not arise from bone) or participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
• Patients unable to comply with the protocol
• Active alcohol or drug abuse
• History of autoimmune disease
• History of allergy to gadolinium or other intravenous (IV) contrast agent, indwelling medical devices or any other condition that would preclude MR scanning
• Patients requiring the ongoing use of dexamethasone, anti-histamines, anti-hypertensives or medications for the control of cardiac failure such as diuretics, where there was likely to be a need for alteration of dose during the study period. Dose adjustment of such medications may have independently altered vascular permeability or blood flow