Fluorouracil and Irinotecan With or Without Leucovorin Compared With Observation in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer - Full Text View

Sponsored by:	Federation Francophone de Cancerologie Digestive
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00091312

Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known whether combination chemotherapy is more effective than observation alone in treating patients who have undergone surgery for colon cancer.

PURPOSE: This randomized phase III trial is studying irinotecan and fluorouracil with or without leucovorin to see how well they work compared to observation alone in treating patients who have undergone surgery for stage II colon cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Procedure: adjuvant therapy	Phase III

MedlinePlus related topics: Cancer Colorectal Cancer Surgery

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Irinotecan U 101440E Irinotecan hydrochloride Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase III Intergroup Trial in Resected Stage 2 (Dukes B) Colon Cancer: 6-Month Infusional 5FU-CPT11 (+/- Folinic Acid) Versus Observation - Determination of Biologic Predictive and Response Factors

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

Primary Outcome Measures:

Disease-free survival at 5 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival at 8 years [ Designated as safety issue: No ]
Tolerability [ Designated as safety issue: Yes ]
Correlation of clinical, histological, and biological prognostic factors with outcome [ Designated as safety issue: No ]

Estimated Enrollment:	1976
Study Start Date:	June 2004

Detailed Description:

OBJECTIVES:

Primary

Compare 5-year disease-free survival in patients with resected stage II adenocarcinoma of the colon treated with adjuvant chemotherapy comprising fluorouracil and irinotecan with or without leucovorin calcium vs no adjuvant therapy.

Secondary

Compare 8-year overall survival in patients treated with these regimens.
Compare tolerability of these regimens in these patients.
Correlate clinical, histological, and biological prognostic factors with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (pT3 vs pT4), pathological differentiation (poorly or undifferentiated vs well or moderately differentiated), and microsatellite instability (positive vs negative vs unknown).

Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients are further randomized to receive 1 of 3 adjuvant chemotherapy regimens.
- Regimen A: Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1, 15, and 29. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Regimen B: Patients receive irinotecan IV over 30-90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 24 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Regimen C: Patients receive irinotecan IV over 60 minutes followed by fluorouracil IV continuously over 48 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients undergo observation only. Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 1,976 patients (988 per treatment arm [247 each in regimens A and B of arm I and 494 in regimen C of arm I]) will be accrued for this study within 4.5 years.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon
- Stage II disease (pT3, N0 or pT4, N0)
  - Penetration of the subserosa or serosa
  - No lymph node metastases
    - At least 12 lymph nodes analyzed
More than 1 synchronous primary colon tumor allowed
- Staging determined for the more advanced tumor
Curative radical resection within the past 2-8 weeks required
- Proximal, distal, and radical margins must be free of tumor (R0 resection)
No rectal tumors
- Gross distal margin of the primary tumor must lie above the peritoneal reflection
No known familial adenomatous polyposis
No hereditary nonpolyposis colorectal cancer
No distant metastases

PATIENT CHARACTERISTICS:

Age

18 to 75

Performance status

WHO 0-1

Life expectancy

Not specified

Hematopoietic

Granulocyte count ≥ 2,000/mm^3
Platelet count ≥ 100,000mm^3
Hemoglobin ≥ 10 g/dL

Hepatic

Bilirubin < 1.25 times upper limit of normal (ULN)
No known Gilbert's syndrome

Renal

Creatinine < 1.25 times ULN

Cardiovascular

No severe or uncontrolled coronary disease
No severe heart failure
No uncontrolled arterial hypertension
No myocardial infarction within the past year
No cerebral vascular accident within the past year
Cardiac arrhythmia allowed provided patient is on proper anticoagulation therapy* NOTE: *Aspirin is not considered proper anticoagulation

Gastrointestinal

No Gardner's syndrome
No Turcot's syndrome
No Crohn's disease
No ulcerative colitis

Other

No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
No other serious disease
No contraindication to any study drugs
No known allergy to leucovorin calcium
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for up to 6 months after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy

Surgery

See Disease Characteristics

Other

No other concurrent anticancer therapy
No concurrent vitamin supplements containing folic acid

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091312

Locations

Egypt
National Cancer Institute - Cairo
Cairo, Egypt
France
Centre Hospitalier Universitaire Ambroise Pare - Boulogne
Boulogne Billancourt, France, F-92104
Hopital Du Bocage
Dijon, France, 21034
Germany
Medizinische Klinik I
Dresden, Germany, D-01307
Italy
Azienda Ospedaliero Careggi
Florence, Italy, 50139
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
Universita Degli Studi di Florence - Policlinico di Careggi
Florence, Italy, 50139
Portugal
Instituto Portugues de Oncologia Centro do Porto, S. A.
Porto, Portugal, 4200-072
Spain
Hospital Universitario de Elche
Elche Alicante, Spain, E-03203

Sponsors and Collaborators

Federation Francophone de Cancerologie Digestive

Investigators

Study Chair:

Laurent Bedenne, MD

Hopital Du Bocage

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000387797, FFCD-EORTC-40012, EORTC-40012, PETACC-4
Study First Received:	September 7, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00091312 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II colon cancer
adenocarcinoma of the colon

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Colonic Diseases
Irinotecan
Leucovorin
Rectal Diseases
Vitamins
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Adjuvants, Immunologic
Trace Elements

Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin
Folic Acid
Calcium, Dietary
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Colonic Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Irinotecan
Physiological Effects of Drugs
Leucovorin
Rectal Diseases
Neoplasms by Site
Vitamins
Therapeutic Uses
Micronutrients

Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Antineoplastic Agents, Phytogenic
Colonic Neoplasms

ClinicalTrials.gov processed this record on May 06, 2009