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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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, i
Sponsor: University of Southern California

Current Primary Outcome:

  • Progression‐free survival during the first phase of the study [ Time Frame: Period from the start of ziv‐aflibercept to the date of radiographic or clinical progression, death, or within 30 days off treatment ]
    Point and precision estimates, median and its 95% confidence interval (CI) will be provided. To examine associations between biomarkers and PFS1, the difference in progression-free survival by each biomarker level will be detected.
  • Progression‐free survival during the second phase of the study [ Time Frame: Period from the start of fluorouracil with ziv-aflibercept to the date of radiographic or clinical progression, death, or within 30 days off treatment ]
    Using the Simon's 2‐stage optimum design, there is a 90% power to detect improvement of adding fluorouracil to ziv‐aflibercept on PFS2 and the type I error rate is 2.3%. Point and precision estimates, median and its 95% CI will be provided.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Overall survival (OS) [ Time Frame: Period from treatment initiation with single agent ziv‐aflibercept to death, assessed up to 3 years ]
    OS will be summarized with Kaplan‐Meyer plots to describe the outcome of patients treated on this protocol.
  • Response rate assessed using Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 3 years ]
    Response rates will be calculated as the percent of evaluable patients whose best response is a complete response or partial response, and exact 95% confidence intervals will be calculated for this estimate.
  • Incidence of adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Within 30 days of the last administration of the study drug ]
    Toxicities observed at each leg of the study will be summarized in terms of type (organ affected, laboratory determination), severity (by NCI Common Toxicity Criteria and nadir or maximum values for the laboratory measures), time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by leg and by course of therapy.


Original Secondary Outcome: Same as current

Information By: University of Southern California

Dates:
Date Received: September 4, 2014
Date Started: March 2015
Date Completion: March 2018
Last Updated: May 4, 2015
Last Verified: May 2015