701P - Phase Ib trial to evaluate capecitabine (C), erlotinib (E), and bevacizumab (B) in patients (pts) with unresectable and/or metastatic pancreatic ca...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Pharmacology
Pancreatic Cancer
Translational Research
Presenter Christian Dittrich
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors C. Dittrich1, P. Buchner2, A. Sahmanovic2, R. Königsberg3, M. Lichtneckert4, G. Nirnberger5, M. Czejka2, K. Geissler6
  • 1Centre For Oncology And Haematology, Kaiser Franz Josef-spital, Ludwig Boltzmann Institute for Applied Cancer Research - LBC-TO and Applied Cancer Research - Institution for Translational Research Vienna, 1100 - Vienna/AT
  • 2Center Of Pharmacy, University Of Vienna, Division of Clinical Pharmacy and Diagnostics, Vienna/AT
  • 3Centre For Oncology And Haematology, Kaiser Franz Josef-spital, Ludwig Boltzmann Institute for Applied Cancer Research - LBC-TO and Applied Cancer Research - Institution for Translational Research Vienna, Vienna/AT
  • 4Centre For Oncology And Haematology, Kaiser Franz Josef-spital, Ludwig Boltzmann Institute for Applied Cancer Research - LBC-TO, Vienna/AT
  • 5Bioconsult Ltd, Bioconsult Ltd, Breitenfurt/AT
  • 6Hospital Hietzing, Ludwig Boltzmann Institute for Clinical Oncology and Photodynamic Therapy - LBC-TO, Vienna/AT

Abstract

Aim

UMPC represents an unmet therapeutic need. Maximum tolerated dose (MTD), PK, safety, and doses recommended for phase II (RPIID) of CEB were determined, and the prognostic potential of CTCs was assessed. (EudraCT 2008-004444-36).

Methods

A 3 + 3 design was used with stepwise dose escalation (DE) starting with C until reaching MTD followed by DE of E and B of one step each. C, E, and metabolites were measured with HPLC. CTCs were determined by anti-EpCAM immunomagnetic enrichment technology.

Results

30 out of 35 pts (15 f, 15 m) aged 63.9 + /-8.4 yrs, with ECOG status 0 (77%) or 1 (23%) and unresectable (N = 1)/metastatic disease (N = 29) were evaluable for MTD. C (mg/m2 bid) was started with 500 (dose level (DL) 1; N = 7), escalated to 650 (DL2; N = 6), 800 (DL3; N = 8), and reached MTD with 900 (DL4; N = 8). At DL5 (N = 3), C 800 was combined with E, escalated from 100 to 150mg po d. At DL6 (N = 3), C and E dosages were kept, B was escalated from 5 to 10mg/kg q 2wks. Whereas DLTs in form of diarrhea (N = 2), erythema, herpes, rectal bleeding, and hand-foot syndrome (N = 1 each) were found during DE of C in DL1 (1 pt), DL2 (1 pt), DL3 (1 pt), and DL4 (3 pts), no further DLT was observed with the DE of E and B. Overall, 264 cycles were applied. Extensive PK could not verify modulation of E by C. Due to the different modes of activation and metabolization of C and E, a PK interaction seems not to be probable. High inter-individual variability of PKs was detected. The most severe G3/4 toxicities per pt were: hand-foot syndrome (16.7%), diarrhea, hyperbilirubinemia, rash/acne (10% each), myocardial infarction, paronychia, cheilitis, anemia (3.3% each). 2 pts (7%) reached PR, 17 pts (61%) had stable disease. PFS was median 3.6 mos (1.3-19.2), OS was median 6.8 mos (1.8-34.0+). No CTC (CTC-) was detected in 13 pts, 1-4 CTCs (CTC+) in 11 pts. PFS in CTC- was median 9.6 mos (95%CI 5.2, 13.9), in CTC+ median 2.8 mos (95%CI 1.4, 4.2); this difference revealed a trend (p = 0.079; Breslow).

Conclusions

RPIID is C 800mg/m2 bid, E 150mg po d and B 10mg/kg q 2wks. CEB can be applied safely and has demonstrated clinical activity.

Disclosure

C. Dittrich: received honoraria from Roche Austria; the research institute directed by CD received unrestricted research grants from Roche Austria; G. Nirnberger: received honoraria / consultation fees from Roche Austria; M. Czejka: The working group directed by MC received grants/research support from Roche Austria; K. Geissler: The research institute directed by KG received grants/research support from Roche Austria. All other authors have declared no conflicts of interest.