Phase I Dose Escalation Trial to Determine the Maximum Tolerated Dose of BIBF 1120 in Combination With Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in Patients With a First, Second or Third Platinum Sensitive Relapse of Advanced Epithelial Ovarian Cancer, Fallopian Tube or Primary Peritoneal Cancer
1. Female patients, age 18 years or older, with a first, second or third relapse of
histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian
tube carcinoma or primary peritoneal cancer
2. Up to three lines of prior chemo (chemotherapy before and after interval surgery to
be counted as one line therapy), with treatment free interval of > 6 months (= time
between last administration of prior anti-cancer treatment, including chemotherapy,
hormonal therapy, or radiation therapy, and diagnosis of progressive disease)
3. Platinum based chemo in immediately preceding line
4. Eligibility for treatment with i.v. chemotherapy regimen of carboplatin AUC 5 and PLD
30 mg/m2 every 4 weeks
5. Life expectancy of at least 3 months
6. Written informed consent that is consistent with International Conference of
Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines
7. Eastern Cooperative Oncology Group (ECOG) performance score 0 or1
8. Prior treatment with angiogenesis inhibitor (bevacizumab, TKI inhibiting VEGFR-2) is
allowed provided treatment with bevacizumab has been discontinued = 28 days prior to
start of therapy and treatment with the TKI has been discontinued = 3 months prior to
start of therapy, provided anti-angiogenic therapy was added to only one of the
preceding lines of therapy
1. Prior chemotherapy with doxorubicin (any formulation, liposomal or non-liposomal
2. Any contraindications for therapy with PLD or carboplatin, e.g. a history of
hypersensitivity reactions to platinum-containing compounds and their excipients.
3. Hypersensitivity to active substance or to any of the excipients of BIBF 1120.
4. Treatment with other investigational drugs or participation in another clinical trial
testing a drug within the past four weeks before start of therapy or concomitantly
with this trial (exception: for previous treatment with angiogenesis inhibitors, cf.
inclusion criterion #8).
5. Laboratory values indicating an increased risk for adverse events.
6. Major surgery within 4 weeks prior to start of study treatment.
7. Patients for whom surgery is planned, e.g. interval debulking surgery.
8. Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone
9. Clinical symptoms or signs of gastrointestinal obstruction that require parenteral
nutrition or hydration.
10. Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug.
11. History of clinical symptoms of brain metastases.
12. Prior thrombosis or thromboembolic event in the presence of an inherited
13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid
haemorrhage within the past 6 months.
14. Known inherited or acquired bleeding disorder.
15. Significant cardiovascular diseases.
16. Serious infections in particular if requiring systemic antibiotic (antimicrobial,
antifungal) or antiviral therapy.
17. Other malignancy diagnosed within the past 5 years.
18. Known serious illness or concomitant non-oncological disease.
19. Patients unable to comply with the protocol.
20. Patients with preserved reproductive capacity who are sexually active and unwilling
to use a medically acceptable method of contraception.
21. Pregnancy or breast feeding.