Galunisertib and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer
Status:
Withdrawn
Trial end date:
2020-06-01
Target enrollment:
Participant gender:
Summary
Part I of this study is designed to identify the recommended phase 2 dose (RP2D) of the
combination regimen of galunisertib/capecitabine as second line treatment in patients with
5-FU or capecitabine resistant CRC. Part II is designed to obtain proof of principle of the
galunisertib plus capecitabine combination in patients with chemo-resistant CRC. The
combination of galunisertib plus capecitabine will be given as second line therapy in the
phase II part of this study.
Patients with chemotherapy resistant activated TGF-β signature-like tumors will have received
a fluoropyrimidine (5FU or capecitabine) in the first line of chemotherapy, usually combined
with oxaliplatin and, depending upon local hospital preferences or national guidelines, also
bevacizumab, or cetuximab/panitumumab if the tumor is KRAS wild type. Addition of
galunisertib to capecitabine should thus result in reversal of unresponsiveness, which is the
first step in exploring this concept in the clinic. Capecitabine can be used as single agent
in advanced CRC and is thus attractive for this study concept. If proof of principle is
achieved also other tumor types can be explored with this genetic makeup, such as non-small
cell lung cancer (NSCLC) in second line of treatment after platinum doublet therapy in first
line, usually cisplatin/carboplatin-pemetrexed in non-squamous and
cisplatin/carboplatin-gemcitabine or cisplatin/carboplatin-paclitaxel in squamous type NSCLC.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
The Netherlands Cancer Institute
Collaborators:
Agendia Azienda Ospedaliera Niguarda Cà Granda Catalan Institute of Health Eli Lilly and Company European Organisation for Research and Treatment of Cancer - EORTC Fundación para la Investigación del Hospital Clínico de Valencia Universitaire Ziekenhuizen Leuven University of Campania "Luigi Vanvitelli" University of Turin, Italy Vall d'Hebron Institute of Oncology