Dose Escalation Study of BIBF 1120 in Patients With Advanced Gynaecological Malignancies

This is an interventional treatment trial for Genital Neoplasms, Female Read More

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