GYN 4: phase I study of BIBF 1120 in combination with paclitaxel/carboplatin in patients with advanced gynecological malignancies

Aims: BIBF 1120 is an angiokinase inhibitor targeting VEGFR, PDGFR, FGFR kinases. Maximal tolerated dose (MTD), safety, and pharmacokinetics (PK) of twice daily BIBF 1120 in combination with carboplatin AUC 5 and paclitaxel 175mg/m² q21 (CP) was evaluated in advanced gynecological malignancies.

Methods: 6 courses of CP and escalating bid doses of BIBF 1120 (2×100mg to 2×250mg) on the days without i.v. chemotherapy were administered. A 3+3 dose escalation design was followed. Additionally, 6 pts were treated on the MTD level.

Results: Twenty-two pts were treated with at least one cycle of CP and BIBF 1120. At 2×250mg of BIBF 1120, two pts developed reversible CTCAE °3/4 elevations of transaminases in the first treatment course. MTD was determined as 200mg BIBF 1120 bid for the combination with CP. Within other dose cohorts (2×100mg, n=3, 2×150mg, n=4, 2×200mg, 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 °3 toxicities were: diarrhea (n=4), ascites (n=1), dyspnoe (n=1), nausea (n=3). In PK profiles of carboplatin, paclitaxel, and BIBF 1120 there was no significant change of the individual and geometric mean plasma concentrations of C and P before and after 3 weeks of continuous bid dosing with BIBF 1120 visible.

Conclusions: BIBF 1120 can be given safely at a dose of 200mg bid together with standard doses of CP without any interaction as shown in PK analyses.

Angiokinaseinhibitor - Gynäkologische Malignome - Phase 1 Studie