To Determine the Maximum Tolerated Dose (MTD) of BIBF 1120 in Patients With Solid Tumours

An Open Label Dose Escalation Study of BIBF 1120 Administered Orally for Four Weeks in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit

The primary objective of this study was to determine the maximum tolerated dose (MTD) of BIBF 1120 in patients with solid tumours by the monitoring of drug-related adverse events. Secondary objectives were the evaluation of safety, efficacy, pharmacokinetics, and pharmacodynamics.

Inclusion Criteria:

• 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 are not amenable to established forms of treatment
• Evaluable tumour deposits by one or more techniques (X-ray, CT, MRI, ultrasound)
• Age 18 years or older
• Life expectancy of at least three months
• Patients had to give written informed consent (which must be consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) and local legislation)
• Eastern Cooperative Oncology Group (ECOG) performance score < 2
• Full recovery from all therapy-related toxicities from previous chemo-, hormone-,immuno-, or radiotherapy

Exclusion Criteria:

• History of relevant surgical procedures during the last four weeks prior to treatment with the trial drug, or active ulcers, or injuries with incomplete wound healing
• Pregnancy or breastfeeding
• Active infectious disease
• 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, International System of Units (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 (> 132 μmol / L, SI unit equivalent)
• Uncontrolled, severe hypertension
• Gastrointestinal disorders anticipated to interfere with the resorption of the study drug
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
• Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
• Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
• Patients unable to comply with the protocol
• Active alcohol or drug abuse