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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 safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00541112
Recruitment Status : Terminated (Toxicity and lack of efficacy)
First Posted : October 8, 2007
Last Update Posted : February 11, 2020
Information provided by (Responsible Party):

Brief Summary:

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 or disease Intervention/treatment 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

Detailed Description:



  • 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).


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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).
Actual Study Start Date : October 29, 2007
Actual Primary Completion Date : January 29, 2010
Actual Study Completion Date : January 29, 2010

Primary Outcome Measures :
  1. Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI

Secondary Outcome Measures :
  1. Preoperative clinical response
  2. Progression-free survival
  3. Overall survival
  4. Early toxicity before surgery
  5. Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
  6. Late toxicity
  7. Late radiotherapy toxicity by CTC AE v. 3.0
  8. Objective response of measurable metastases by RECIST
  9. Sexual function
  10. Downstaging and downsizing of patients with operable disease
  11. Surgical complications
  12. Sphincter function
  13. Predictive biomarkers of response to cetuximab

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00541112

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Institut Bergonie
Bordeaux, France, 33076
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Oscar Lambret
Lille, France, 59020
Centre Leon Berard
Lyon, France, 69373
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
Centre Antoine Lacassagne
Nice, France, 06189
Centre Hospitalier Lyon Sud
Pierre Benite, France, 69495
Centre Rene Huguenin
Saint Cloud, France, 92210
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Institut Gustave Roussy
Villejuif, France, F-94805
Sponsors and Collaborators
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Principal Investigator: David Azria, MD, PhD Institut du Cancer de Montpellier - Val d'Aurelle
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Responsible Party: UNICANCER Identifier: NCT00541112    
Other Study ID Numbers: CDR0000565937
FRE-FNCLCC-ACCORD-14/0604 ( Other Identifier: FNCLCC )
2006-003336-30 ( EudraCT Number )
First Posted: October 8, 2007    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
stage III rectal cancer
stage IV rectal cancer
adenocarcinoma of the rectum
Additional relevant MeSH terms:
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Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Protective Agents
Vitamin B Complex