Radiation Therapy, Chemotherapy, and Cetuximab Followed by Surgery, Chemotherapy, and Cetuximab in Treating Patients With Locally Advanced or Metastatic Rectal Cancer That Can Be Removed by Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00541112
First received: October 5, 2007
Last updated: February 19, 2009
Last verified: October 2007
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, 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 cetuximab, 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 radiation therapy together with combination chemotherapy and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and cetuximab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II clinical trial is studying how well giving radiation therapy together with chemotherapy and cetuximab followed by surgery, chemotherapy, and cetuximab works in treating patients with locally advanced or metastatic rectal cancer that can be removed by surgery.


Condition Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-Surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Preoperative clinical response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Early toxicity before surgery [ Designated as safety issue: Yes ]
  • Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery) [ Designated as safety issue: Yes ]
  • Late toxicity [ Designated as safety issue: Yes ]
  • Late radiotherapy toxicity by CTC AE v. 3.0 [ Designated as safety issue: Yes ]
  • Objective response of measurable metastases by RECIST [ Designated as safety issue: No ]
  • Sexual function [ Designated as safety issue: No ]
  • Downstaging and downsizing of patients with operable disease [ Designated as safety issue: No ]
  • Surgical complications [ Designated as safety issue: No ]
  • Sphincter function [ Designated as safety issue: No ]
  • Predictive biomarkers of response to cetuximab [ Designated as safety issue: No ]

Estimated Enrollment: 103
Study Start Date: July 2007
Detailed Description:

OBJECTIVES:

Primary

  • Determine the complete remission rate at 6 months after neoadjuvant radiotherapy, capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).

Secondary

  • Determine progression-free survival.
  • Determine overall survival.
  • Assess toxicities.
  • Evaluate objective response in patients with measurable metastases.
  • Determine the rate of local recurrence.
  • Evaluate the downstaging and downsizing of patients with operable disease.
  • Evaluate surgical complications in patients with operable disease.
  • Evaluate biological markers predictive of response to cetuximab.

OUTLINE: This is a multicenter study.

  • Neoadjuvant therapy: Patients undergo radiotherapy for 5 weeks and receive concurrent oral capecitabine twice daily on days 1-5 of each week and oxaliplatin IV over 2 hours on day 1 of each week (XELOX). Patients also receive cetuximab IV on day 1 of the first week and on days 1-7 of weeks 2-5.
  • Surgery: At 6 weeks after completing chemoradiotherapy, patients with resectable disease undergo surgery comprising total mesorectal excision. Patients with progressive disease, nonresectable tumor, or who require R2 surgery are removed from the study.
  • Adjuvant therapy: Patients who undergo surgery, with or without removal of metastases, receive FOLFOX 4, comprising oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours, and leucovorin calcium IV on day 1, and cetuximab IV. Treatment repeats every 2 weeks for up to 6 courses (approximately 3 months). Patients who have not undergone prior surgical resection of metastases may have surgery to remove metastases after completing this second regimen of chemotherapy.

After completion of study therapy, patients are followed periodically for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the rectum

    • Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease

      • Metastases must be resectable
    • Primary tumor examined by endorectal echography and MRI
  • Measurable disease by thoraco-abdomino-pelvic scanner
  • Disease considered susceptible to treatment with radiotherapy and chemotherapy
  • No diffuse metastases considered nonresectable
  • No acute occlusion not caused by colostomy

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-2
  • WBC ≥ 4,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • Creatinine ≤ 130 µmol/L
  • Transaminases ≤ 5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients of must use effective contraception

Exclusion criteria:

  • Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or radiotherapy
  • Impossible to perform translational analyses
  • Uncontrolled severe illness
  • Severe renal or hepatic insufficiency
  • Cardiac insufficiency or symptomatic coronary disease
  • Sensitive peripheral neuropathy
  • Uncontrolled diabetes
  • Other malignancy within the past 10 years except previously treated basal cell skin cancer or carcinoma in situ of the cervix
  • Impossible to participate in study due to geographic, social, or psychiatric reasons
  • Patients who are under supervision or incarcerated

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior anticancer chemotherapy or radiotherapy for this cancer
  • No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids, or allopurinol
  • No concurrent participation in another therapeutic study or receiving another experimental drug
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541112

Locations
France
Institut Bergonie Recruiting
Bordeaux, France, 33076
Contact: Marianne Fonck, MD    33-5-5633-3242      
Centre de Lutte Contre le Cancer Georges-Francois Leclerc Recruiting
Dijon, France, 21079
Contact: Philippe Maingon, MD    33-380-737-517    mcperrin@dijon.fnclcc.fr   
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Xavier Mirabel    33-3-2029-5521      
Centre Leon Berard Recruiting
Lyon, France, 69373
Contact: Isabelle Martel Lafay, MD    33-4-7878-5166      
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle Recruiting
Montpellier, France, 34298
Contact: David Azria, MD, PhD    33-4-6761-3132    David.Azria@valdorel.fnclcc.fr   
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Contact: Eric Francois    33-4-9203-1613      
Centre Hospitalier Lyon Sud Recruiting
Pierre Benite, France, 69495
Contact: Jean-Christophe Saurin    33-4-7886-1289      
Centre Rene Huguenin Recruiting
Saint Cloud, France, 92210
Contact: Frederique B. Cvitkovic, MD    33-1-4711-1515    f.cvitkovic@stcloud-huguenin.org   
Centre Alexis Vautrin Recruiting
Vandoeuvre-les-Nancy, France, 54511
Contact: Thierry Conroy, MD    33-3-8359-8460      
Institut Gustave Roussy Recruiting
Villejuif, France, F-94805
Contact: Patrick Ezra, MD    33-1-4211-4125      
Sponsors and Collaborators
UNICANCER
Investigators
Principal Investigator: David Azria, MD, PhD Centre Val d'Aurelle - Paul Lamarque
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00541112     History of Changes
Other Study ID Numbers: CDR0000565937, FRE-FNCLCC-ACCORD-14/0604, EU-20759, EUDRACT-2006-003336-30
Study First Received: October 5, 2007
Last Updated: February 19, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage III rectal cancer
stage IV rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Cetuximab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on August 21, 2014