Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC)

• Frequency and intensity of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and changes in safety laboratory parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Potential pharmacokinetic (PK) drug-drug interaction between BIBF 1120 and a combined administration of PLD and carboplatin [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Progression-free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Time to tumour progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Objective tumour response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Duration of objective tumour response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Serological progression-free interval (based on CA-125 mesurements) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

This phase I, open label dose escalation study will investigate the addition of BIBF 1120 to treatment with the combination of carboplatin and Pegylated Liposomal Doxorubicin (PLD) in patients with advanced, platinum sensitive relapsed ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer. Patients will be treated with BIBF 1120 together with carboplatin and PLD in up to 6-9 repeated 28 days treatment courses until disease progression is observed.

• Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
  BIBF 1120 towice daily along with standard therapy of PLD + CBDCA
• Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
  BIBF 1120 towice daily along with standard therapy of PLD + CBDCA
• Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
  BIBF 1120 towice daily along with standard therapy of PLD + CBDCA

• Experimental: BIBF 1120 (low) + Carboplatin + PLD
  BIBF 1120 (low dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
  Intervention: Drug: BIBF 1120 (low) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
• Experimental: BIBF 1120 (medium) + Carboplatin + PLD
  BIBF 1120 (medium dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
  Intervention: Drug: BIBF 1120 (medium) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min
• Experimental: BIBF 1120 (high) + Carboplatin + PLD
  BIBF 1120 (high dose) + carboplatin (AUC5 mg/mL*min) + PLD (30 mg/m2)
  Intervention: Drug: BIBF 1120 (high) + PLD 30 mg/m2 + CBDCA AUC5 mg/mL*min

Inclusion criteria:

1. Female patients, age 20 years or older, with relapse of histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer
2. Up to 3 lines of prior chemo therapy, with treatment free interval of >6 months
3. Platinum based chemotherapy in the immediately preceding line.
4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
5. Written informed consent that is consistent with Good Clinical Practice (GCP) guidelines

Exclusion criteria:

1. Prior chemotherapy with PLD, and any contraindication for therapy with carboplatin or PLD.
2. More than 2 lines of prior therapies that contained angiogenesis inhibitor.
3. Patients for whom surgery is planned, e.g. interval debulking surgery.
4. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
5. Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy.
6. Laboratory values indicating an increased risk for adverse events.
7. Significant cardiovascular diseases.