Neoplasms

Symptoms and General Pathology

All Conditions

Infections

Digestive System Diseases

Neoplasm Metastasis

Peritonitis

Colorectal Neoplasms

Carcinoma

Peritoneal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Abdominal Neoplasms

Peritoneal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Antimetabolites

Galunisertib 150 mg BID for 14 days in a 28-day cycle plus capecitabine 1000 mg/m2 BID for 14 days in a 28-day cycle

Combination therapy with galunisertib plus capecitabine

Galunisertib plus capecitabine

Alaa Embaby, MD

Neeltje Steeghs, MD, PhD

Tineke Buffart, MD, PhD

Louis Vermeulen, MD, PhD

This is a two-center open-label non-randomized proof of principle study consisting of a dose-finding part (phase I) and phase II study with Simon two-stage design investigating the anti-tumor activity of the combination of capecitabine and galunisertib in patients with colorectal cancer with peritoneal metastases.

This is a two-center pharmacological open-label non-randomized proof of principle study consisting of two parts: a phase I study evaluating the RP2D of galunisertib in combination with capecitabine; and a phase II study investigating the anti-tumor activity and safety of galunisertib in combination with capecitabine in advanced colorectal cancer (CRC) with peritoneal metastases (PM).

In phase II of the study a Simon two-stage design will be used. 15 patients will be treated with the galunisertib/capecitabine combination. If at least 2 out of 15 patients respond, an additional cohort of 10 patients will be included to a total of 25 patients. With 6 or more responses, the treatment will be declared to be of sufficient activity and with 5 or less it will be declared of insufficient activity.

The galunisertib dose will be 150 mg twice daily (BID) for the first 14 days of every 4-week cycle, which is the maximum tolerated dose when given as single agent (except of day 1 of cycle 1: single dose of galunisertib 150 mg for PK analysis, from day 2: 150 mg BID).

Capecitabine will be dosed during every 14-day on time of galunisertib at 1000 mg/m2 BID, which is the labelled dose as monotherapy and will in case of toxicities be reduced according to standard care.

Clinical assessments will be performed routinely to monitor safety. Anti-tumor activity will be measured by CT scan according to RECIST 1.1 criteria. Tumor biopsies will be obtained for exploratory objectives.

Galunisertib Combined With Capecitabine in Advanced CRC With PM

Phase I/II Study With Galunisertib Combined With Capecitabine in Patients With Advanced Chemotherapy Resistant Colorectal Cancer With Peritoneal Metastases

To determine the safety and RP2D of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with peritoneal metastases

To determine the anti-tumor activity as measured by ORR of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with PM.

Time from first response until progression

Time from start of treatment until first objective response

Time from start of the treatment until progression

Exploratory genomic analyses to determine biomarkers for response and resistance to the combination of galunisertib and capecitabine

Spots Global Cancer Trial Database for peritonitis carcinomatosa