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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00349076
First received: July 5, 2006
Last updated: July 1, 2014
Last verified: July 2014

July 5, 2006
July 1, 2014
July 2006
December 2014   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00349076 on ClinicalTrials.gov Archive Site
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 ]
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Not Provided
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Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy With 5-Fluorouracil and Oxaliplatin Versus 5-Fluorouracil Alone in Rectal Cancer
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Rectal Neoplasms
  • 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; Calciumfolinate: 400 mg/m² on day 1; 5-Fluorouracil: 2400 mg/m² continuous infusion for 46 hours repeat day 15, 8 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

  • Experimental: 1

    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

    Intervention: Drug: 5-FU and oxaliplatin
  • Active Comparator: 2

    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

    Intervention: Drug: 5-FU

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1200
December 2015
December 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00349076
CAO/ARO/AIO-04, German Cancer Aid (no. 106759)
Not Provided
University of Erlangen-Nürnberg Medical School
University of Erlangen-Nürnberg Medical School
Not Provided
Principal Investigator: Rolf Sauer, M.D. Dept. of Radiation Therapy, University of Erlangen, Germany
University of Erlangen-Nürnberg Medical School
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP