Abstract
3561 Background: BIBF 1120 is an oral triple angiokinase inhibitor targeting VEGFR, PDGFR, FGFR kinases which might be interesting targets for gynecologic tumor therapy. Therefore, we performed a phase I study to evaluate maximal tolerated dose (MTD), safety, and pharmacokinetics (PK) of twice daily BIBF 1120 in combination with carboplatin AUC 5 and paclitaxel 175 mg/m2 q21 (CP) in patients with advanced or recurrent gynecological malignancies. Methods: 6 courses of CP and escalating bid doses of BIBF 1120 (2x100 mg to 2x250 mg) on the days without i.v. chemotherapy were administered. A 3 + 3 dose escalation design was followed. An additional cohort of 6 pts was treated on the MTD level. Results: Twenty-three pts were enrolled and 21 pts were treated with at least one cycle of CP and BIBF 1120. At 2x250 mg of BIBF 1120, two pts developed reversible CTCAE °3 and °4 elevations of AST and ALT in the first treatment course. MTD was determined as 200 mg BIBF 1120 bid for the combination with CP. Within the other dose cohorts (2x100 mg, n= 3, 2x150 mg, n= 4, 2x200 mg, n= 13) no dose limiting toxicities were observed. There was no increase in hematological toxicity with the addition of BIBF 1120 compared to standard CP. Further non-hematological °3 toxicities were: diarrhea (n=4), ascites (n=1), dyspnoe (n=1), nausea (n=3).Thus far, the PK profiles of carboplatin, paclitaxel, and BIBF 1120 have been evaluated in seven pts (2x100 mg, n=3 and 2x150 mg, n=4). There was no significant change of the individual and geometric mean plasma concentrations of C and P before and after 3 weeks of continuous daily bid dosing with BIBF 1120. Conclusions: BIBF 1120 can be given safely at a dose of 200 mg bid together with standard doses of CP in pts with advanced gynecological malignancies. Preliminary PK analyses did not reveal any interaction of CP and BIBF 1120. [Table: see text]
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