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

Rectal Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00349076
• Other study ID #: CAO/ARO/AIO-04
• Secondary ID: German Cancer Ai
• Status: Completed
• Phase: Phase 3
• First received: July 5, 2006
• Last updated: July 29, 2016
• Start date: July 2006
• Est. completion date: June 2016

Study information

• Verified date: July 2016
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1256
• Est. completion date: June 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Rectal Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
Germany	Kreiskliniken Altötting-Burghausen	Altötting
Germany	Gesundheitszentrum St. Marien	Amberg
Germany	Onkologische Gemeinschaftspraxis	Ansbach
Germany	Krankenhaus Marienwörth	Bad Kreuznach
Germany	Caritas-Krankenhaus	Bad Mergentheim
Germany	Onkologische Schwerpunktpraxis	Bad Soden
Germany	Klinik Bad Trissl-Oberaudorf	Bad Trissl
Germany	Klinikum Bayreuth GmbH	Bayreuth
Germany	Aerzteforum Hennigsdorf	Berlin
Germany	Städtische Kliniken	Bielefeld
Germany	St.-Agnes-Hospital Bocholt	Bocholt
Germany	Ruhr-Universität Bochum; Knappschaftskrankenhaus	Bochum
Germany	St. Josef-Hospital	Bochum
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Onkologische Praxis	Buchholz
Germany	Praxis für Hämatologie und Onkologie	Burgwedel
Germany	Klinikum Coburg gGmbH	Coburg
Germany	Onkologisches Versorgungszentrum Rehling-Donauwörth-Dachau	Donauwörth
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Katholisches Krankenhaus St. Nepomuk	Erfurt
Germany	Dept. of Radiation Therapy, University of Erlangen	Erlangen
Germany	Alfried Krupp Krankenhaus	Essen
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum Esslingen a.N.	Esslingen
Germany	Universitätsklinikum	Frankfurt/Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Weisseritztal-Kliniken	Freital
Germany	Kliniken an der Paar, Krankenhaus Friedberg	Friedberg
Germany	Klinikum Fulda	Fulda
Germany	SRH-Waldklinikum	Gera
Germany	Wilhelm-Anton-Hospital	Goch
Germany	Klinik am Eichert	Göppingen
Germany	Georg-August-Universität Göttingen	Göttingen
Germany	Universitätsklinikum Greifswald	Greifswald
Germany	St. Elisabeth und St. Barbara Krankenhaus	Halle
Germany	Asklepios Klinik Hamburg-Harburg	Hamburg
Germany	Diakonie Klinikum Hamburg	Hamburg
Germany	Praxis für Hämatologie und Onkologie, Hamm	Hamm
Germany	Marienhospital	Herne
Germany	Onkologische Schwerpunktpraxis	Hildesheim
Germany	Universitätsklinikum des Saarlandes	Homburg/Saar
Germany	Klinik für Knochenmarkstransplantation und Hämatologie/Onkologie GmbH	Idar-Oberstein
Germany	Klinikum der Friedrich Schiller Universität	Jena
Germany	Innere Medizin, Hämatologie und Int. Onkologie	Kassel
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Gemeinschaftspraxis für Hämatologie und Internistische Onkologie	Köln
Germany	Praxis für Hämatologie und Onkologie	Köln
Germany	Onkologische Schwerpunktpraxis	Kronach
Germany	Gemeinschaftspraxis Onkologie	Landshut
Germany	Klinikum Landshut	Landshut
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	Universitätsklinikum - St. Hildegardis-Krankenhaus Mainz	Mainz
Germany	Phillips-Universität Marburg	Marburg
Germany	Kliniken Maria Hilf	Mönchengladbach
Germany	Gemeinschaftspraxis Onkologie	Muhr am See
Germany	Klinikum rechts der Isar, Technische Universität	München
Germany	Universitätsklinikum Großhadern	München
Germany	Clemenshospital Münster	Münster
Germany	Universitätsklinikum Münster	Münster
Germany	Klinikum Schwäbisch Gmünd, Stauferklinik	Mutlangen
Germany	Hämatologisch-onkologische Schwerpunktpraxis Northeim	Northeim
Germany	Klinikum Nürnberg	Nürnberg
Germany	Darmzentrum Ortenau	Offenburg
Germany	Klinikum Oldenburg; Pius Hospital Oldenburg	Oldenburg
Germany	Paracelsus-Krankenhaus Ruit	Ostfildern
Germany	St. Vincenz Krankenhaus	Paderborn
Germany	Klinikum Passau	Passau
Germany	St. Josefs Krankenhaus	Potsdam
Germany	Krankenhaus Barmherzige Brüder	Regensburg
Germany	Schwerpunktpraxis für Hämatologie und Onkologie mit Tagesklinik	Regensburg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Klinikum Rosenheim	Rosenheim
Germany	Medizinische Fakultät der Universität Rostock	Rostock
Germany	Kreiskrankenhaus Rottweil	Rottweil
Germany	Thüringen-Kliniken Saalfeld-Rudolstadt	Saalfeld
Germany	Hämatologisch-Onkologische Schwerpunktpraxis	Singen
Germany	Onkologische Praxisgemeinschaft Stade	Stade
Germany	Klinikum Traunstein	Traunstein
Germany	Onkologische Schwerpunktpraxis Traunstein	Traunstein
Germany	Krankenhaus der Barmherzigen Brüder	Trier
Germany	Universitätsklinikum Ulm	Ulm
Germany	Marienhaus Klinikum, St. Elisabeth Klinik Saarlouis, St. Michael Krankenhaus Völklingen	Völklingen
Germany	Klinikum Wetzlar-Braunfels	Wetzlar
Germany	Asklepios Paulinen Klinik	Wiesbaden
Germany	Reinhard-Nieter-Krankenhaus	Wilhelmshaven
Germany	Juliusspital	Wuerzburg
Germany	Missionsärztliche Klinik	Würzburg
Germany	Universitätsklinikum Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3 years	No
Secondary	Resection rate, rate of sphincter preservation, tumor regression, cumulative incidence of local and distant recurrences, overall survival, toxicity, quality of life		5-year follow up	No