dose escalation study of bibf 1120 in patients with advanced gynaecological malignancies

Conditions: Genital Neoplasms, Female

Summary: the primary objectives of this trial were to determine the safety, tolerability, and mtd of bibf 1120 when added to standard therapy with carboplatin and paclitaxel


Eligibility criteria:
inclusion criteria: * female patients with the following histologically confirmed advanced gynaecological malignancies: epithelial ovarian cancer, endometrial carcinoma, uterine sarcoma, mixed müllerian tumour, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma or vulvular carcinoma * metastatic disease or locally advanced disease that is not resectable with curative intention * indication for combination chemotherapy with paclitaxel/carboplatin as judged by the investigator * age 18 years or older * eastern cooperative oncology group (ecog) performance status 0 or 1 * life expectancy of at least 6 months * written informed consent that is not consistent with ich-gcp (international conference on harmonisation - good clinical practice) guidelines and local requirements exclusion criteria: * participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study * radiotherapy within 4 weeks before the start of therapy * chemotherapy, immunotherapy or hormonal therapy (with the exception of hormonal replacement therapy) within 4 weeks before the start of the therapy * patients with germ cell tumours, early stage ovarian cancer (fédération internationale de gynécologie et d'obstétrique \[figo\] stage i-iia), primary cervical cancer (figo i-iii), primary endometrial cancer (figo i-iii) or borderline tumours * patients with known brain metastases * symptomatic bowel obstruction or known or suspected malabsorption * patients with pericardial effusion which is haemodynamically relevant * other malignancy diagnosed within the past 5 years (other than non-melanomatous skin cancer or cervical carcinoma in situ) * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study medication * history of haemorrhagic or thrombotic event (including transient ischemic attacks) in the past 6 months * concurrent therapeutic anticoagulation or anti-platelet therapy (except chronic low dose daily acetylsalicylic acid \<300 mg) * major injuries and surgeries within the past 3 weeks, planned surgical procedures during the trial, incomplete wound healing * known hypersensitivity to paclitaxel, carboplatin, bibf 1120 or any of their excipients or vehicles such as polyoxyethylated castor oil * clinically significant peripheral polyneuropathy (\>ctcae grade 1) which precludes therapy with paclitaxel * absolute neutrophil count (anc) \<1500/μl, platelet count \<100000/μl, or haemoglobin \<9 mg/dl * total bilirubin \>1.5 mg/dl (26 μmol/l), alt (alanine aminotransferase) and/or ast (aspartate aminotransferase) \>1.5 x the upper limit of normal (uln) * serum creatinine \>1.5 mg/dl (\>132 μmol/l) * persistent gross haematuria * pregnancy or breast feeding * women with childbearing potential and who are sexually active and unwilling to use a medically acceptable method of contraception (oral contraceptive, diaphragm with spermicide, intrauterine device, condom with spermicide) * known or suspected active drug or alcohol abuse