Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery
Summary
RATIONALE: Drugs used in chemotherapy, such as 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. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective with or without panitumumab in treating patients with colon cancer.
PURPOSE: This randomized phase III trial is studying giving fluorouracil together with oxaliplatin and panitumumab to see how well it works compared with giving fluorouracil and oxaliplatin without panitumumab in treating patients with high-risk colon cancer that can be removed by surgery.
Description
OBJECTIVES:
Primary
- To determine if neoadjuvant chemotherapy with or without panitumumab followed by deferred surgery and completion of chemotherapy postoperatively can reduce the 2-year recurrence as compared to surgery and postoperative chemotherapy with or without panitumumab.
- To determine if adding panitumumab in the neoadjuvant treatment produces a measurable increase in antitumor efficacy as measured by tumor shrinkage.
Secondary
- To assess the accuracy of pre-treatment CT scan staging.
- To assess the tolerability of the neoadjuvant therapies.
- To assess the nature and frequency of surgical complications.
- To measure the impact of the treatments on quality of life and on resource usage.
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 year vs 50-59 years vs 60-69 years vs ≥ 70 years), radiological T-stage (T3 vs T4), radiological nodal status (Nx vs N0 vs N1 vs N2), site of primary tumor, proposed chemotherapy (OxMdG vs OxCap), and defunctioning colostomy (yes vs no).
Patients receive 1 of the 2 following treatment regimens:
- OxMdG: Patients receive oxaliplatin IV and folinic acid IV over 2 hours followed by fluorouracil IV continuously over 46 hours on day 1 for 1 course.
- OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 for 1 course.
Patients are then randomized to 1 of 2 treatment arms.
- Neoadjuvant therapy:
- Arm I: Patients receive 1 of the following chemotherapy regimens:
- OxMdG: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
- OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive 1 of the following regimens:
- OxMdG + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1 followed by oxaliplatin IV over 2 hours and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
- OxCap + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1 followed by oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Approximately 52 days after beginning chemotherapy, patients in both arms proceed to surgery.
- Surgery: Patients in both arms undergo surgical resection of the primary tumor.
- Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive adjuvant treatment on the same arm for which they received neoadjuvant therapy.
- Arm I: Patients receive either nine 2-week courses of OxMdG therapy or six 3-week courses of OxCap therapy.
- Arm II: Patients receive twelve 2-week courses of OxMdG therapy concurrently with panitumumab given every 2 weeks OR eight 3-week courses of OxCap therapy concurrently with panitumumab given every 3 weeks.
Tumor tissue is collected during surgery and blood samples are collected periodically for biomarker studies. Samples are analyzed for the detection of k-ras mutations; the detection of EGFR expression and/or functional genetic polymorphisms of the EGFR gene via PCR; the detection of copy number EGFR gene amplification via fluorescence in situ hybridization (FISH); the detection of EGFR activation via immunohistochemistry (IHC); the detection of EGFR by downstream parameters via western blotting and/or gene expression microarray techniques; for proteomics; and for epigenetics.
Patients complete quality of life questionnaires at baseline, at first course of postoperative chemotherapy, and at 1 year following randomization.
After completion of study treatment, patients are followed every 6 months for 3 years and then annually thereafter.
Study Design
Allocation: Randomized, Control: Active Control, Primary Purpose: Treatment
Conditions
Colorectal Cancer
Intervention
panitumumab, capecitabine, fluorouracil, oxaliplatin, fluorescence in situ hybridization, gene expression analysis, microarray analysis, polymerase chain reaction, proteomic profiling, western blotting, immunohistochemistry staining method, adjuvant thera
Location
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham
England
United Kingdom
B15 2TH
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00647530
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
In Situ Hybridization, Fluorescence
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Spectral Karyotyping
The simultaneous identification of all chromosomes from a cell by fluorescence in situ hybridization (IN SITU HYBRIDIZATION, FLUORESCENCE) with chromosome-specific florescent probes that are discerned by their different emission spectra.
Molecular Diagnostic Techniques
MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.
Gene Transfer Techniques
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
Oligonucleotide Probes
Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.
Clinical Trials
The purpose of this interventional study is to investigate whether there is evidence that panitumumab in combination with XELOX (capecitabine plus oxaliplatin) chemotherapy will safely inc...
RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, capecitabine, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Co...
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as...
The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer
A Study of Xeloda (Capecitabine) Plus Oxaliplatin in Patients With Colon Cancer
This 2 arm study will compare the efficacy and safety of intermittent oral Xeloda plus Eloxatin (oxaliplatin) with that of fluorouracil/leucovorin in patients who have had surgery for colo...
PubMed Articles
Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer.
Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer Original Article, N Engl J Med 2009;360:563-572. In the introduction (page 564), the second sentence should have read, "The com...
PURPOSE Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting ep...
PURPOSE: The aims of this study is to determine the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) delivered concurrent with radiation therapy (RT) in the treatment of locally advanced...
Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer.
To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection.
PURPOSE: To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, in...
