Clinical Trial: Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Trial Of Neoadjuvant Bevacizumab With Modified FOLFOX7 In Patients With Stage II And III Rectal Cancer

Brief Summary: This phase II trial studies how well bevacizumab, fluorouracil, leucovorin calcium, and oxaliplatin before surgery works in treating patients with stage II-III rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, 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 bevacizumab together with fluorouracil, leucovorin calcium, and oxaliplatin may be an effective treatment for rectal cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine if six cycles of modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX7) plus bevacizumab (Avastin) will yield complete pathologic response (cPR) of 25% or more in the primary tumor of patients with stage II and III rectal cancer.

SECONDARY OBJECTIVES:

I. To assess the rate of tumor regression (pathologic stage lower than clinical stage) after 6 cycles of mFOLFOX7 and bevacizumab in the primary rectal cancer.

II. To assess local recurrence rate over 3 years after 6 cycles of mFOLFOX7 and bevacizumab.

TERTIARY OBJECTIVES:

I. Correlation of the following marker with response (defined as CPR or down staging):

  • Intratumoral Gene expression and germline polymorphism of genes involved in the vascular endothelial growth factor (VEGF) and VEGF independent pathways (VEGF, vascular endothelial growth factor receptor 1 [VEGFR1], VEGFR2, interleukin-8 [IL8], chemokine (C-X-C motif) receptor 2 [CXCR2], intercellular adhesion molecule [ICAM], VEGFR1 and VEGFR2, neuropilin 1 or 2 [NRP1,2], cluster of differentiation [CD] 44, aldehyde dehydrogenase [ALDH], leucine-rich repeats and immunoglobulin-like [LRIG].
  • Circulating tumor cells (CTC) and VEGF-factor A (A) on the CTC.

II. Prediction of surgical resection margin by pretreatment magnetic resonance imaging (MRI).

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 3
Sponsor: University of Southern California

Current Primary Outcome: Rate of CPR in the pathology specimen [ Time Frame: Up to 3 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Tumor regression on mesorectal margins (pathologic stage lower than clinical stage) [ Time Frame: Up to 3 years ]
  • Rate of locoregional recurrence [ Time Frame: Up to 3 years ]
  • Incidence and nature of adverse events (AEs) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 ( v4) [ Time Frame: Up to 3 years ]
  • Incidence and nature of serious AEs (SAEs) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ]
  • Incidence and nature of AEs of special interest for bevacizumab (grades) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ]


Original Secondary Outcome: Same as current

Information By: University of Southern California

Dates:
Date Received: June 4, 2013
Date Started: August 2, 2013
Date Completion: August 2, 2019
Last Updated: April 11, 2017
Last Verified: April 2017