889P - Phase I dose-escalation study to determine the maximum tolerated dose (MTD) of nintedanib (BIBF 1120) in combination with carboplatin/pegylated lip...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer agents
Ovarian Cancer
Therapy
Biological Therapy
Presenter José María Del Campo
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors J.M. Del Campo1, B. Pardo Búrdalo2, V. Rodriguez Freixinos3, L. Gaba Garcia4, M. Gil Martín2, A. Oaknin3, A. Ballester5, M.O. Sailer6, M. Merger7, N. Morsli8, L. Vidal4
  • 1Medical Oncology, Vall d’Hebron University Hospital, 08035 - Barcelona/ES
  • 2Medical Oncology, Institut Catala d’Oncologia, Barcelona/ES
  • 3Medical Oncology, Vall d’Hebron University Hospital, Barcelona/ES
  • 4Medical Oncology, Hospital Clínic i Provincial, 08036 - Barcelona/ES
  • 5Medical, Boehringer Ingelheim España S.A., Barcelona/ES
  • 6Global Biometry & Clin. Applications, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 7Ta Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 8Oncology, Boehringer Ingelheim France S.A.S., Paris/FR

Abstract

Aim

Nintedanib (N) is an oral, triple angiokinase inhibitor of VEGF, PDGF and FGF signalling. A recent study showed that the addition of N to standard 1st-line chemotherapy significantly prolongs PFS (HR 0.84; p = 0.0239) in advanced EOC (epithelial ovarian cancer) pts.1 The current study (NCT01314105; 1199.119) was designed to determine dose-limiting toxicities (DLTs) and MTD of N + carboplatin/PLD in pts with ROC. 1Du Bois A, et al. Int J Gynecol Cancer. 2013;23(8suppl 1):abstract p7.

Methods

This was a dose-escalation study of oral, continuous daily dosing of N (days 2–28) + iv carboplatin/PLD (AUC 5/30 mg/m2) on day 1 in a 28-day cycle in pts with ≤3 lines of therapy for platinum-sensitive ROC. Cohort 1 received 150 mg bid N, which was the starting dose. The other two predefined cohorts were Cohort -1 (100 mg bid N) and Cohort 2 (200 mg bid N); Cohort -1 was not explored because de-escalation to 100 mg was not necessary.

Results

13 pts (Cohort 1: n = 7, median age 63, EOC n = 7; Cohort 2: n = 6, median age 53, EOC n = 5, fallopian tube carcinoma n = 1) were treated and DLTs were noted in 2 of 12 evaluable pts during the first cycle (Cohort 1: elevated alanine aminotransferase [ALT], 1 pt; Cohort 2: elevated ALT and aspartate aminotransferase [AST], 1 pt). The MTD of N was determined to be 200 mg bid + carboplatin/PLD (AUC 5/30 mg/m2). The most frequent drug-related Grade ≥3 adverse events (AEs) in Cohort 1 were elevated ALT, AST and gamma − glutamyltransferase (GGT) (14.3% each) and in Cohort 2 were elevated ALT (50.0%), AST (33.3%) and GGT (33.3%); neutropenia (33.3%); decreased haemoglobin (16.7%); and diarrhoea (16.7%). The elevated ALT case in Cohort 1 was a serious AE. All CTCAE Grade 3 events were manageable with basic supportive care, temporary treatment interruptions and N dose reductions.

Conclusions

The MTD of N was 200 mg bid with carboplatin/PLD (AUC 5/30 mg/m2), and none of the pts discontinued the trial because of safety reasons. This combination exhibited a favourable safety profile with no unexpected AEs in pts with platinum-sensitive ROC. An expansion cohort study of six additional patients treated at the MTD is currently ongoing.

Disclosure

A. Ballester: Employee: Boehringer Ingelheim España S.A., Spain; M.O. Sailer: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany; M. Merger: Employee: Boehringer Ingelheim Pharma GmbH KG, Germany; N. Morsli: Employee: Boehringer Ingelheim France S.A.S., France. All other authors have declared no conflicts of interest.