Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Rectal Adenocarcinoma Clinical Trial

Official title: A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer

Status Completed

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of nintedanib when given together with capecitabine and to see how well they work in treating patients with colorectal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also block the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nintedanib with capecitabine may be a better treatment for colorectal cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

• I. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of nintedanib when administered with capecitabine within the study population and, establish the recommended phase II dose (RP2D). (Phase I)

• II. To assess progression free survival at 18 weeks. (Phase II)

SECONDARY OBJECTIVES:

• I. To assess median progression free survival. (Phase II)

• II. To assess median overall survival from the date of enrollment to the time of death will be documented. (Phase II)

• III. To assess the objective response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. (Phase II)

• IV. To assess the toxicity of dose regimen using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase II)

TERTIARY OBJECTIVES:

• I. Measurement of circulating angiogenic cytokines (CAFs): vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR) 1/2, placental growth factor (PlGF), granulocyte macrophage colony-stimulating factor (GMCSF), leptin, interleukin (IL)-1 alpha (a), IL-8, IL-6, fibroblast growth factor basic (FGFb), osteopontin and pentraxin-3. (Phase II)

• II. Measurement of drug levels and pharmacokinetic (PK)/pharmacodynamic (PD) modeling. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of nintedanib followed by a phase II study.

Patients receive capecitabine orally (PO) twice daily (BID) (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 28 days until resolution or satisfactory stabilization of persistent drug-related toxicity, and then every 6 months thereafter. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Colon Adenocarcinoma
• Colonic Neoplasms
• Rectal Adenocarcinoma
• Rectal Neoplasms
• Recurrent Colon Carcinoma
• Recurrent Rectal Carcinoma
• Stage IVA Colon Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Rectal Cancer

• NCT number: NCT02393755
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 8, 2015
• Completion date: May 18, 2021