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 - Full Text View

Sponsored by:	Federation Nationale des Centres de Lutte Contre le Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00541112

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	Drug: capecitabine Drug: cetuximab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Capecitabine Fluorouracil Oxaliplatin Calcium gluconate Cetuximab Liothyronine sodium Triiodothyronine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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).

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

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

Locations

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

Sponsors and Collaborators

Federation Nationale des Centres de Lutte Contre le Cancer

Investigators

Principal Investigator:

David Azria, MD, PhD

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000565937, FRE-FNCLCC-ACCORD-14/0604, EU-20759, EUDRACT-2006-003336-30
Study First Received:	October 5, 2007
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00541112
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage III rectal cancer
stage IV rectal cancer
adenocarcinoma of the rectum

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Leucovorin
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Rectal neoplasm
Calcium, Dietary
Oxaliplatin
Digestive System Diseases
Fluorouracil
Neoplasm Metastasis
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on January 14, 2009