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
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

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: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
Germany
Kreiskliniken Altötting-Burghausen
Altötting, Germany, 84503
Gesundheitszentrum St. Marien
Amberg, Germany, 92224
Onkologische Gemeinschaftspraxis
Ansbach, Germany, 91522
Krankenhaus Marienwörth
Bad Kreuznach, Germany, 55543
Caritas-Krankenhaus
Bad Mergentheim, Germany, 97980
Onkologische Schwerpunktpraxis
Bad Soden, Germany, 65812
Klinik Bad Trissl-Oberaudorf
Bad Trissl, Germany, 83080
Klinikum Bayreuth GmbH
Bayreuth, Germany, 95445
Aerzteforum Hennigsdorf
Berlin, Germany, 16761
Städtische Kliniken
Bielefeld, Germany, 33604
St.-Agnes-Hospital Bocholt
Bocholt, Germany, 46397
St. Josef-Hospital
Bochum, Germany, 44791
Ruhr-Universität Bochum; Knappschaftskrankenhaus
Bochum, Germany, 44892
Klinikum Bremen-Mitte
Bremen, Germany, 28205
Onkologische Praxis
Buchholz, Germany, 21244
Praxis für Hämatologie und Onkologie
Burgwedel, Germany, 30938
Klinikum Coburg gGmbH
Coburg, Germany, 96450
Onkologisches Versorgungszentrum Rehling-Donauwörth-Dachau
Donauwörth, Germany, 86609
Universitätsklinikum Carl Gustav Carus
Dresden, Germany, 01307
Katholisches Krankenhaus St. Nepomuk
Erfurt, Germany, 99097
Dept. of Radiation Therapy, University of Erlangen
Erlangen, Germany, 91054
Alfried Krupp Krankenhaus
Essen, Germany, 45131
Universitätsklinikum Essen
Essen, Germany, 45122
Klinikum Esslingen a.N.
Esslingen, Germany, 73073
Universitätsklinikum
Frankfurt/Main, Germany, 60590
Universitätsklinikum Freiburg
Freiburg, Germany, 79110
Weisseritztal-Kliniken
Freital, Germany, 01705
Kliniken an der Paar, Krankenhaus Friedberg
Friedberg, Germany, 86316
Klinikum Fulda
Fulda, Germany, 36013
SRH-Waldklinikum
Gera, Germany, 07548
Wilhelm-Anton-Hospital
Goch, Germany, 47574
Universitätsklinikum Greifswald
Greifswald, Germany, 17475
Klinik am Eichert
Göppingen, Germany, 73035
Georg-August-Universität Göttingen
Göttingen, Germany, 37075
St. Elisabeth und St. Barbara Krankenhaus
Halle, Germany, 06110
Diakonie Klinikum Hamburg
Hamburg, Germany, 22527
Asklepios Klinik Hamburg-Harburg
Hamburg, Germany, 21075
Praxis für Hämatologie und Onkologie, Hamm
Hamm, Germany, 59071
Marienhospital
Herne, Germany, 44625
Onkologische Schwerpunktpraxis
Hildesheim, Germany, 31134
Universitätsklinikum des Saarlandes
Homburg/Saar, Germany, 66421
Klinik für Knochenmarkstransplantation und Hämatologie/Onkologie GmbH
Idar-Oberstein, Germany, 55743
Klinikum der Friedrich Schiller Universität
Jena, Germany, 07740
Innere Medizin, Hämatologie und Int. Onkologie
Kassel, Germany, 34117
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Kiel, Germany, 24015
Onkologische Schwerpunktpraxis
Kronach, Germany, 96317
Gemeinschaftspraxis für Hämatologie und Internistische Onkologie
Köln, Germany, 51105
Praxis für Hämatologie und Onkologie
Köln, Germany, 50677
Klinikum Landshut
Landshut, Germany, 84034
Gemeinschaftspraxis Onkologie
Landshut, Germany, 84028
Universitätsklinikum Leipzig
Leipzig, Germany, 04103
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Lübeck, Germany, 23538
Universitätsklinikum - St. Hildegardis-Krankenhaus Mainz
Mainz, Germany, 65131
Phillips-Universität Marburg
Marburg, Germany, 35043
Gemeinschaftspraxis Onkologie
Muhr am See, Germany, 91735
Klinikum Schwäbisch Gmünd, Stauferklinik
Mutlangen, Germany, 73557
Kliniken Maria Hilf
Mönchengladbach, Germany, 41061
Klinikum rechts der Isar, Technische Universität
München, Germany, 81675
Universitätsklinikum Großhadern
München, Germany, 81377
Clemenshospital Münster
Münster, Germany, 48149
Universitätsklinikum Münster
Münster, Germany, 48149
Hämatologisch-onkologische Schwerpunktpraxis Northeim
Northeim, Germany, 37154
Klinikum Nürnberg
Nürnberg, Germany, 90419
Darmzentrum Ortenau
Offenburg, Germany, 77654
Klinikum Oldenburg; Pius Hospital Oldenburg
Oldenburg, Germany, 26133
Paracelsus-Krankenhaus Ruit
Ostfildern, Germany, 73760
St. Vincenz Krankenhaus
Paderborn, Germany, 33098
Klinikum Passau
Passau, Germany, 94032
St. Josefs Krankenhaus
Potsdam, Germany, 14471
Universitätsklinikum Regensburg
Regensburg, Germany, 93042
Krankenhaus Barmherzige Brüder
Regensburg, Germany, 93049
Schwerpunktpraxis für Hämatologie und Onkologie mit Tagesklinik
Regensburg, Germany, 93047
Klinikum Rosenheim
Rosenheim, Germany, 83022
Medizinische Fakultät der Universität Rostock
Rostock, Germany, 18059
Kreiskrankenhaus Rottweil
Rottweil, Germany, 78628
Thüringen-Kliniken Saalfeld-Rudolstadt
Saalfeld, Germany, 07318
Hämatologisch-Onkologische Schwerpunktpraxis
Singen, Germany, 78224
Onkologische Praxisgemeinschaft Stade
Stade, Germany, 21680
Klinikum Traunstein
Traunstein, Germany, 83278
Onkologische Schwerpunktpraxis Traunstein
Traunstein, Germany, 83278
Krankenhaus der Barmherzigen Brüder
Trier, Germany, 54292
Universitätsklinikum Ulm
Ulm, Germany, 89081
Marienhaus Klinikum, St. Elisabeth Klinik Saarlouis, St. Michael Krankenhaus Völklingen
Völklingen, Germany, 66333
Klinikum Wetzlar-Braunfels
Wetzlar, Germany, 35578
Asklepios Paulinen Klinik
Wiesbaden, Germany, 65197
Reinhard-Nieter-Krankenhaus
Wilhelmshaven, Germany, 26389
Juliusspital
Wuerzburg, Germany, 97070
Missionsärztliche Klinik
Würzburg, Germany, 97074
Universitätsklinikum Würzburg
Würzburg, Germany, 97080
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
Principal Investigator: Rolf Sauer, M.D. Dept. of Radiation Therapy, University of Erlangen, Germany
  More Information

No publications provided by University of Erlangen-Nürnberg Medical School

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT00349076     History of Changes
Other Study ID Numbers: CAO/ARO/AIO-04, German Cancer Aid (no. 106759)
Study First Received: July 5, 2006
Last Updated: July 1, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014