Neoadjuvant Radiation Therapy and Capecitabine in Treating Patients With Stage III or Stage IV Colorectal Adenocarcinoma

Phase II Study Of Radiotherapy And Capecitabine As Pre-Operative Treatment In Patients With Colorectal Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as capecitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well neoadjuvant radiation therapy and capecitabine work in treating patients who are undergoing surgery for stage III or stage IV colorectal adenocarcinoma.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Radiation: radiation therapy; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: capecitabine

Detailed Description

OBJECTIVES:

Primary

• Determine the objective tumor response rate in patients with stage III or IV colorectal adenocarcinoma treated with neoadjuvant radiotherapy and capecitabine.

Secondary

• Determine the tolerance profile of this regimen in these patients.
• Determine the rate of preservation of functional integrity of the anal sphincter in patients treated with this regimen.
• Compare the conversion rate from the effects of mutilating surgery vs surgery with sphincter preservation in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily and undergo concurrent radiotherapy 5 days a week on weeks 1-5. Patients undergo surgery on week 6.

Patients are followed every 4 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 10 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Dijon, France, 21000
    • Hopital Drevon
  • La Rochelle, France, 17000
    • Hopital Saint - Louis
  • Le Mans, France, 72000
    • Centre Jean Bernard
  • Lyon, France, 69008
    • Clinique Saint Jean
  • Metz, France, 57038
    • Hopital Notre-Dame de Bon Secours
  • Montfermeil, France, 93370
    • Intercommunal Hospital
  • Mulhouse, France, 68051
    • Centre Hospitalier de Mulhouse
  • Paris, France, 75970
    • Hôpital Tenon
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Senlis, France, 60309
    • C.H. Senlis
  • Suresnes, France, 92151
    • Centre Médico-Chirurgical Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal adenocarcinoma

  • Clinical stage T3, T4, N+
• Measurable disease
• Awaiting surgery and likely to benefit from neoadjuvant radiotherapy

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• No hepatic condition that would interfere with study medication

Renal

• Creatinine clearance at least 80 mL/min
• No renal condition that would interfere with study medication

Cardiovascular

• No serious cardiac failure with the past year
• No myocardial infarction within the past year
• No cardiac insufficiency
• No angina
• No uncontrolled arrhythmia
• No uncontrolled hypertension

Gastrointestinal

• No superior intestinal tract malfunction
• No malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent serious infection
• No other serious illness
• No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
• No metabolic condition that would interfere with study medication
• No dementia or altered mental status
• No psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for colorectal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for colorectal cancer

Surgery

• Not specified

Other

• More than 30 days since prior participation in another clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective tumor response rate

Secondary Outcome Measures

Outcome Measure
Tolerability
Rate of preservation of functional integrity of the anal sphincter
Comparison of the conversion rate from the effects of mutilating surgery vs surgery with sphincter preservation

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Olivier Dupuis, MD, Centre Jean Bernard

Publications and helpful links

General Publications

• Dupuis O, Vie B, Lledo G, Hennequin C, Noirclerc M, Bennamoun M, Jacob JH. Preoperative treatment combining capecitabine with radiation therapy in rectal cancer: a GERCOR Phase II Study. Oncology. 2007;73(3-4):169-76. doi: 10.1159/000127383. Epub 2008 Apr 16.

Study record dates

Study Major Dates

• Study Start: January 1, 2002

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 11, 2004
• First Posted (ESTIMATE): January 12, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2009
• Last Update Submitted That Met QC Criteria: February 6, 2009
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CDR0000346895; FRE-GERCOR-R01-01; EU-20329