Overview

This trial is active, not recruiting.

Condition rectal neoplasms
Treatments 5-fu and oxaliplatin, 5-fu
Phase phase 3
Sponsor University of Erlangen-Nürnberg Medical School
Start date July 2006
End date December 2015
Trial size 1200 participants
Trial identifier NCT00349076, CAO/ARO/AIO-04, German Cancer Aid (no. 106759)

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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; Calciumfolinate: 400 mg/m² on day 1; 5-Fluorouracil: 2400 mg/m² continuous infusion for 46 hours; repeat day 15, 8 cycles
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; Calciumfolinate: 400 mg/m² on day 1; 5-Fluorouracil: 2400 mg/m² continuous infusion for 46 hours repeat day 15, 8 cycles
(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
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

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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)

Additional Information

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
Principal investigator Rolf Sauer, M.D.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by University of Erlangen-Nürnberg Medical School.