Trials / Completed

CompletedNCT01652196

Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

A Phase II Study of the Combination of Aflibercept (VEGF-Trap) Plus Modified FOLFOX 6 in Patients With Previously Untreated Metastatic Colorectal Cancer

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 56 (actual)

Sponsor: John Hays · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well giving aflibercept together with combination chemotherapy works in treating patients with previously untreated colon or rectal cancer that is metastatic or locally advanced and cannot be removed by surgery. Aflibercept may stop the growth of colon or rectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving aflibercept together with combination chemotherapy may kill more tumor cells

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the progression free survival (PFS) of patients with untreated metastatic colorectal cancer (mCRC) receiving the combination of modified leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX6) (mFOLFOX6) and aflibercept. SECONDARY OBJECTIVES: I. To evaluate the objective response rate (complete response \[CR\] + partial response \[PR\]) and the disease control rate (CR + PR + stable disease \[SD\]), as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, of patients with untreated mCRC receiving the combination of mFOLFOX6 and aflibercept. II. To evaluate overall survival of patients with untreated mCRC receiving the combination of mFOLFOX6 and aflibercept. III. To further characterize the safety and toxicity of the combination of mFOLFOX6 and aflibercept, including 60 day all-cause mortality. IV. To describe patients with mCRC whose disease is rendered resectable as a consequence of therapy with the combination of mFOLFOX 6 and aflibercept. TERTIARY OBJECTIVES: I. To assess the use of dynamic imaging modalities including dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) to evaluate changes in vascular permeability and FDG avidity and correlate with clinical efficacy (PFS, overall survival \[OS\], and response by RECIST 1.1). II. To evaluate circulating levels of vascular endothelial growth factor A (VEGFA), phosphatidylinositol glycan anchor biosynthesis, class F (PlGF), soluble vascular endothelial growth factor receptor 2 (VEGF-R2), chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) as potential biomarkers for efficacy of aflibercept. III. To evaluate for the presence of VEGF single nucleotide polymorphisms (SNPs) and whether any SNP(s), when detected, may be predictive of efficacy and/or toxicity of aflibercept. IV. To assess microvessel density/tumor blood flow, capillary permeability and vessel normalization by tumor biopsy pre and post treatment with aflibercept. V. To evaluate the presence of hypertension as a predictive biomarker for clinical efficacy of aflibercept. OUTLINE: Patients receive aflibercept intravenously (IV) over 1 hour followed by oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5-15 minutes and then continuously over 46 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	aflibercept	4 mg/kg as a 1-hour IV(intervenous) infusion
DRUG	oxaliplatin	85 mg/m2 IV infused over 2 hours
DRUG	leucovorin	200 mg/m2 (Or levoleucovorin 100 mg/m2. If leucovorin is not available due to drug shortages the regimen should be administered with the leucovorin omitted) IV over 2 hours. Alternatively, leucovorin may be administered (via separate infusion lines) concurrently with oxaliplatin
DRUG	fluorouracil	400 mg/m2 IV bolus over 5-15 minutes, then 2400 mg/m2 continuous IV infusion over 46 hours.
OTHER	Correlative Studies	Patients are required to have tissue available before enrolling on the study. A fresh biopsy is only required if there is insufficient material for analysis. Repeat tumor biopsies after 8 weeks of therapy are optional and will only be performed at the Ohio State University Medical Center.
PROCEDURE	DCE MRI	Images at weeks 0, and after 8 weeks +/- 1 week of treatment (after Cycle 2).
RADIATION	f18FDG-PET	18FDG-PET is a functional imaging technique that relies on tumor uptake of radiolabeled tracer 18 fluorodeoxyglucose (18FDG). FDG-PET is a widely-used imaging modality in the detection and monitoring of a variety of metastatic cancers, including colorectal cancer (99-102).
PROCEDURE	PET (positron emission tomography)	Correlative studies

Timeline

Start date: 2012-11-14
Primary completion: 2019-08-06
Completion: 2022-08-30
First posted: 2012-07-27
Last updated: 2025-02-05
Results posted: 2025-02-05

Locations

6 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT01652196. Inclusion in this directory is not an endorsement.