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

July 29, 2016 updated by: University of Erlangen-Nürnberg Medical School

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1256

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
5-year follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

July 5, 2006

First Submitted That Met QC Criteria

July 5, 2006

First Posted (Estimate)

July 6, 2006

Study Record Updates

Last Update Posted (Estimate)

August 1, 2016

Last Update Submitted That Met QC Criteria

July 29, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAO/ARO/AIO-04
  • German Cancer Aid (no. 106759)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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