Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy With 5-Fluorouracil and Oxaliplatin Versus 5-Fluorouracil Alone in Rectal Cancer - Full Text View

Purpose

Standard treatment for locally advanced cancer of the rectum is preoperative chemoradiotherapy with 5-Fluorouracil (5-FU) plus 4 cycles of postoperative chemotherapy with 5-FU. According to our previous study (CAO/ARO/AIO-94, published in the New England Journal of Medicine 2004; 351:1731-40) this treatment results in only 6% of local failures, yet, still 36% of all patients develop distant metastasis. Therefore, our new study (CAO/ARO/AIO-04) incorporates new drugs, i.e. 5-FU + oxaliplatin, in an effort to improve the control of distant metastases. It is our hypothesis that the rate of disease free survival will improve by 5 to 8% after 3 years of follow-up.

Condition	Intervention	Phase
Rectal Neoplasms	Drug: 5-FU and oxaliplatin Drug: 5-FU	Phase III

MedlinePlus related topics:

Cancer

ChemIDplus related topics:

Fluorouracil Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study

Official Title:	Prospective Randomised Multicenter Phase-III-Study: Preoperative Radiochemotherapy and Adjuvant Chemotherapy With 5-Fluorouracil Plus Oxaliplatin Versus Preoperative Radiochemotherapy and Adjuvant Chemotherapy With 5-Fluorouracil for Locally Advanced Rectal Cancer

Further study details as provided by University of Erlangen-Nürnberg:

Primary Outcome Measures:

Disease free survival at 3 years defined as the interval from randomization to locoregional or metastatic recurrence or the appearance or a secondary colorectal cancer or death, whichever occurs first. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Resection rate, rate of sphincter preservation, tumor regression, cumulative incidence of local and distant recurrences, overall survival, toxicity, quality of life [ Time Frame: 5-year follow up ] [ Designated as safety issue: No ]

Estimated Enrollment:	1200
Study Start Date:	July 2006
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Preoperative simultaneous radiochemotherapy: 5-Fluorouracil und Oxaliplatin: Radiotherapy starts on day 1 of chemotherapy; 28 fractions; single dose: 1,8 Gy once per day, monday through friday; Total dose: 50,4 Gy; Oxaliplatin: 50 mg/m² i.v., days 1, 8, 22 und 29; 5-Fluorouracil: 250 mg/m²/d continuous infusion, days 1-14 and 22-35 Adjuvant Chemotherapy: Oxaliplatin: 100 mg/m² i.v. on day 1; Calciumfolinat: 400 mg/m² on day 1; 5-Fluorouracil: 2400 mg/m² continuous infusion for 46 hours; repeat day 15, 8 cycles	Drug: 5-FU and oxaliplatin Preoperative radiochemotherapy: Oxaliplatin: 50 mg/m² i.v., days 1, 8, 22 und 29; 5-Fluorouracil: 250 mg/m²/d continuous infusion, days 1-14 and 22-35 Adjuvant Chemotherapy: Oxaliplatin: 100 mg/m² i.v. on day 1; Calciumfolinat:400 mg/m² on day 1; 5-Fluorouracil: 2400 mg/m² continuous infusion for 46 hours repeat day 15, 8 cycles
2: Active Comparator Preoperative simultaneous radiochemotherapy: 5-Fluorouracil Radiotherapy starts on day 1 of chemotherapy; 28 fractions; single dose: 1,8 Gy once per day, monday through friday; Total dose: 50,4 Gy; 5-Fluorouracil: Days 1-5 and 29-33: 120h-continuous infusion 1000 mg/m²/d Adjuvant Chemotherapy: 5-Fluorouracil: 500 mg/m² on 5 consecutive days (day 1-5) i.v. bolus fot 2-5 minutes; repeat day 29, 4 cycles	Drug: 5-FU Preoperative radiochemotherapy: 5-Fluorouracil: Days 1-5 and 29-33: 120h-continuous infusion 1000 mg/m²/d Adjuvant Chemotherapy: 5-Fluorouracil: 500 mg/m² on 5 consecutive days (day 1-5) i.v. bolus fot 2-5 minutes; repeat day 29, 4 cycles

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Minimum age: 18 years
Histologically proven, advanced primary carcinoma of the rectum (tumor ? 12cm from the anal verge, with clinically staged T3/4 or any node-positive disease
No prior therapy except a diverting stoma
ECOG PS less than or equal 2
Adequate bone marrow function: Leukocytes > 3,5 x 10^9/L Absolute neutrophil count > 1,5 x 10^9/L Platelet count > 100 x 10^9/L Hemoglobin > 10 g/dl
Adequate hepatic function: Total bilirubin < 2,0 mg/dl ALAT, ASAT, alkaline phosphatase, gamma-GT < 3 x ULN 7. Serum creatinine < 1,5 mg/dl, creatinine-clearance > 50 ml/min
Written informed consent before randomization

Exclusion Criteria:

Pregnant or breast feeding women
Fertile patients without adequate contraception during therapy
Past or ongoing drug abuse or alcoholic excess
Prior chemotherapy
Prior radiotherapy to the pelvis
Prior (within 4 weeks) or concurrent treatment with any other investigational agent
Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
History of severe somatic or psychological diseases: - instable cardiac disease not well controlled with medication, myocardial infarction within the last 6 months:* Central nervous system disorders or psychiatric disability including dementia or epileptic disease; * active uncontrolled intercurrent infections or sepsis
Peripheral neuropathy > 2 (NCI CTC AE grading)
Previous or concurrent malignancies, with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix. The inclusion of patients with other adequately treated tumors within the last 5 years has to be discussed with the principal investigator
Chronic diarrhea (> NCI CTC AE-Grad 1)
Known allergy to substances containing platinum compounds
Concurrent use of the antiviral agent sorivudine or chemically related analogues
Known deficiency of dehydropyrimidindehydrogenase (DPD)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00349076

Contacts


Contact: Rolf Sauer, M.D.	0049-9131-85 ext 33968	st-studiensekretariat@uk-erlangen.de

Contact: Studiensekretariat	0049-9131-85 ext 33968	st-studiensekretariat@uk-erlangen.de

Show 77 Study Locations

Sponsors and Collaborators

University of Erlangen-Nürnberg

Investigators


Principal Investigator:	Rolf Sauer, M.D.	Dept. of Radiation Therapy, University of Erlangen, Germany

More Information

Responsible Party:	University-Hospital of Erlangen-Nürnberg, Department for Radiooncology ( Prof. Dr. R. Sauer )
Study ID Numbers:	CAO/ARO/AIO-04, German Cancer Aid (no. 106759)
First Received:	July 5, 2006
Last Updated:	June 13, 2008
ClinicalTrials.gov Identifier:	NCT00349076
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Study placed in the following topic categories:

Digestive System Neoplasms

Rectal Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Intestinal Neoplasms

Rectal neoplasm

Oxaliplatin

Digestive System Diseases

Fluorouracil

Gastrointestinal Neoplasms

Rectal cancer

Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites

Neoplasms

Antimetabolites, Antineoplastic

Neoplasms by Site

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Therapeutic Uses

Physiological Effects of Drugs

Immunosuppressive Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 10, 2008

Sponsored by:	University of Erlangen-Nürnberg
Information provided by:	University of Erlangen-Nürnberg
ClinicalTrials.gov Identifier:	NCT00349076