Ziv-Aflibercept Followed by Ziv-Aflibercept, Fluorouracil, and Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer

Recurrent Rectal Cancer Clinical Trial

Official title: Phase II Study of Ziv-Aflibercept Followed by the Addition of 5-FU in the Third Line Setting of Metastatic Colorectal Cancer

Status Withdrawn

Clinical Trial Summary

This phase II trial studies how long it takes colorectal cancer resistant to standard treatment to grow while receiving treatment with ziv-aflibercept, and how well adding fluorouracil and leucovorin calcium to ziv-aflibercept works in treating patients with stage IV colorectal cancer after they progress on ziv-aflibercept alone. Ziv-aflibercept may stop the growth of colorectal cancer by blocking the formation of tumor blood vessels. Fluorouracil and leucovorin calcium are drugs used in chemotherapy. Fluorouracil works to stop the growth of tumors cells by preventing the cells from growing and dividing. Leucovorin calcium helps fluorouracil work better. Adding fluorouracil and leucovorin calcium to ziv-aflibercept may be an effective treatment for patients who progress on ziv-aflibercept alone.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the progression‐free survival during the first phase of the study (PFS1) in patients with metastatic colorectal cancer treated with single agent ziv‐aflibercept after progressing on leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX) and leucovorin calcium, fluorouracil, irinotecan hydrochloride (FOLFIRI) with bevacizumab +/‐ cetuximab or panitumumab.

II. To determine the progression‐free survival (PFS2) in patients with metastatic colorectal cancer treated with ziv‐aflibercept and 5‐fluorouracil (fluorouracil), after progressing on ziv‐aflibercept alone.

SECONDARY OBJECTIVES:

I. Overall survival. II. Response rate. III. Incidence and nature of adverse events. IV. Growth modulation index (ratio of PFS2/PFS1).

TERTIARY OBJECTIVES:

I. To determine relevant biomarkers which can distinguish patients with a progression free survival greater than 3 months on single agent ziv‐aflibercept (tumor vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor [VEGFR]1 and 2, baseline plasma phosphatidylinositol glycan anchor biosynthesis, class F [PlGF]).

II. Plasma levels of VEGF‐A, B, C, D, intercellular adhesion molecule 1 (ICAM), chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) (Gro alpha), hepatocyte growth factor (HGF), stem cell growth factor beta (SCGF beta) prior to treatment and with each cycle of therapy.

III. Single nucleotide polymorphisms (SNPs) of VEGFA, VEGFR1 & 2 & 3, interleukin (IL)8, angiopoietin-2 (Ang2), IL‐6, ICAM, PlGF, neuropilin (NRP)1 & 2, chemokine (C-X-C motif) receptor 2 (CXCR2) and others in the angiogenic pathway.

IV. Tumor messenger ribonucleic acid (mRNA) expression levels of VEGF B, C, D, VEGFR 3; NRP 1, 2, and VEGF isoforms on biopsy specimens taken at trial initiation and upon disease progression and addition of 5‐FU.

V. Correlation of biomarkers with toxicity of ziv‐aflibercept alone and with 5‐FU.

OUTLINE:

PHASE I: Patients receive ziv‐aflibercept intravenously (IV) over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of progression, patients proceed to Phase II.

PHASE II: Patients receive ziv‐aflibercept IV over 1 hour, leucovorin calcium IV over 1 minute, and fluorouracil IV over 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Mucinous
• Colorectal Neoplasms
• Cystadenocarcinoma
• Mucinous Adenocarcinoma of the Colon
• Mucinous Adenocarcinoma of the Rectum
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Signet Ring Adenocarcinoma of the Colon
• Signet Ring Adenocarcinoma of the Rectum
• Stage IVA Colon Cancer
• Stage IVA Rectal Cancer
• Stage IVB Colon Cancer
• Stage IVB Rectal Cancer

• NCT number: NCT02235324
• Study type: Interventional
• Source: University of Southern California
• Status: Withdrawn
• Phase: Phase 2
• Start date: March 2015
• Completion date: March 2018