Clinical Trial: Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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 Summary:

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 biosyn
Sponsor: Kristen Ciombor

Current Primary Outcome: Proportion of patients alive and progression-free [ Time Frame: At 15 months from initiation of therapy ]

Assuming that the number of treatment successes (alive and progression-free) is binomially distributed, proportion estimates along with their corresponding exact 95% confidence intervals will be calculated.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Objective response rate (ORR) defined as the proportion of patients who achieve a PR or CR based on RECIST 1.1 criteria divided by the total number of evaluable patients [ Time Frame: Up to 4 weeks post-treatment ]
    Summarized as a proportion with corresponding 95% confidence interval.
  • Percentage of patients able to undergo surgery [ Time Frame: Up to 4 weeks post-treatment ]
    Summarized as a proportion with corresponding 95% confidence interval.
  • Progression free survival (PFS) [ Time Frame: From study entry to the time of progressive disease and/or death, assessed up to 4 weeks post-treatment ]
    Will be evaluated using the methods of Kaplan and Meier.
  • Overall survival [ Time Frame: From study entry to time of death due to any cause, assessed up to 4 weeks post-treatment ]
    Will be evaluated using the methods of Kaplan and Meier.
  • Incidence of severe (grade 3+) adverse events or toxicities, assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 4 weeks post-treatment ]
  • Tolerability in terms of number of patients who require dose modifications and/or dose delays [ Time Frame: Up to 4 weeks post-treatment ]
  • Proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 4 weeks post-treatment ]


Original Secondary Outcome:

  • Objective response rate (ORR) defined as the proportion of patients who achieve a PR or CR based on RECIST 1.1 criteria divided by the total number of evaluable patients [ Time Frame: Up to 4 weeks post-treatment ]
    Summarized as a proportion with corresponding 95% confidence interval.
  • Percentage of patients able to undergo surgery [ Time Frame: Up to 4 weeks post-treatment ]
    Summarized as a proportion with corresponding 95% confidence interval.
  • PFS [ Time Frame: From study entry to the time of progressive disease and/or death, assessed up to 4 weeks post-treatment ]
    Will be evaluated using the methods of Kaplan and Meier.
  • Overall survival [ Time Frame: From study entry to time of death due to any cause, assessed up to 4 weeks post-treatment ]
    Will be evaluated using the methods of Kaplan and Meier.
  • Incidence of severe (grade 3+) adverse events or toxicities, assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 4 weeks post-treatment ]
  • Tolerability in terms of number of patients who require dose modifications and/or dose delays [ Time Frame: Up to 4 weeks post-treatment ]
  • Proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 4 weeks post-treatment ]


Information By: Ohio State University Comprehensive Cancer Center

Dates:
Date Received: July 25, 2012
Date Started: November 14, 2012
Date Completion: September 1, 2018
Last Updated: January 25, 2017
Last Verified: January 2017