Galunisertib and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer

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.

Conditions

• Colorectal Cancer Metastatic

Interventions

DRUG

Galunisertib

treatment with capecitabine and galunisertib

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology

  collaborator OTHER

• Agendia

  collaborator INDUSTRY

• European Organisation for Research and Treatment of Cancer - EORTC

  collaborator NETWORK

• Azienda Ospedaliera Niguarda Cà Granda

  collaborator OTHER

• Fundación para la Investigación del Hospital Clínico de Valencia

  collaborator OTHER

• University of Campania Luigi Vanvitelli

  collaborator OTHER

• University of Turin, Italy

  collaborator OTHER

• Eli Lilly and Company

  collaborator INDUSTRY

• Catalan Institute of Health

  collaborator OTHER_GOV

• Universitaire Ziekenhuizen KU Leuven

  collaborator OTHER

• The Netherlands Cancer Institute

  lead OTHER

Principal Investigators

• J Tabernero, Prof · VHIO

• R Salazar, MD, PhD · ICO

• R Bernards, Prof · Agendia

• S Siena, Prof · ONCG

• A Cervantes, Prof · Instituto de Investigacion Sanitaria INCLIVA

• F Ciardiello, Prof · Unina2

• A Bardelli, Prof · UNITO

• S Tejpar, Prof · UZ Leuven

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-08-24

Primary Completion

2020-06-01

Completion

2020-06-01

Countries

• Netherlands

Study Locations