Capecitabine in the Perioperative Treatment of Rectal Cancer (Rektum-III)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01500993
Recruitment Status : Completed
First Posted : December 29, 2011
Last Update Posted : December 29, 2011
Information provided by (Responsible Party):
Frederik Wenz, Universitätsmedizin Mannheim

Brief Summary:
This study compares capecitabine with standard 5-FU in the perioperative treament of locally advanced rectal cancer.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: Capecitabine Drug: 5-FU Phase 3

Detailed Description:

5-Fluorouracil (5-FU) based chemoradiotherapy (CRT) is regarded a standard perioperative treatment in locally advanced rectal cancer (LARC). We investigate the replacement of 5-FU by the oral pro-drug capecitabine (cape) within a randomized phase III trial. Patients aged ≥18 years with LARC stage II or III are recruited into this two-arm, two-cohort randomized non-inferiority phase-III trial (arm A: cape, arm B: 5-FU; cohort [C] I: adjuvant, C II: neoadjuvant). Regimens: Arm A: CRT: 50.4 Gy + cape 1,650 mg/m² days 1-38 plus five cycles of cape 2,500 mg/m² d 1-14, repeated d 22 (C I: 2 x cape, CRT, 3 x cape; C II: CRT, TME surgery followed by cape x 5). Arm B: CRT: 50.4 Gy + infusional 5-FU 225 mg/m² daily [C I] or infusional 5-FU 1,000 mg/m² d 1-5 and 29-33 [C II] plus 4 cycles of bolus 5-FU 500mg/m² d 1-5, repeated d 29 (C I: 2 x 5-FU, CRT, 2 x 5-FU; C II: CRT, TME surgery followed by 5-FU x 4). Primary endpoint is 5-year overall survival (OS), secondary endpoints comprise 3-year disease-free survival (DFS) and safety.

The study is designed to investigate whether 5- year overall survival rate (SR5) is non-inferior in arm A versus arm B. We hypothesize that SR5 in the standard arm B is 57.5%. Sample size calculation is performed with a power of 80% and a type I error of 5% and with a drop-out rate of 5%. Therefore, a total of at least 372 evaluable patients (i.e. 186 per arm) is required to confirm non-inferiority of the experimental arm A with a non-inferiority margin of maximal 12.5% and a median follow-up time of 48 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 401 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial
Study Start Date : March 2002
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 5-Fluorouracil (5-FU)
Drug - 5FU based chemoradiotherapy and chemotherapy
Drug: 5-FU
4 cycles of bolus 5-FU (500 mg/sqm) and 1 cylce of 5-Fu based chemoradiotherapy (either 1,000 mg/sqm/day infusional 5-Fu days 1-5 and 29-33 or 225 mg/sqm/day infusional 5-Fu throughout the time of chemoradiotherapy)
Other Name: 5-Fluorouracil

Experimental: Capecitabine
Drug - Capecitabin-based radiochemotherapy and chemotherapy
Drug: Capecitabine
Capecitabine standard therapy (i.e. 2,500 mg/sqm) x 5 cycles plus 1 cycle of capecitabine based chemoradiotherapy (1.650 mg/sqm)
Other Name: Xeloda

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 5-year ]

Secondary Outcome Measures :
  1. disease-free survival (DFS) [ Time Frame: 3-year DFS ]
  2. Local recurrence rate [ Time Frame: 5 years ]
    Percentage of patient with local recurrence

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Eligible patients are 18 years or older and have histologically confirmed adenocarcinoma of the rectum (defined as the distal border of the tumour less than 16 cm from the anal verge measured by rigid rectoscopy) with no evidence of distant metastases (identified by abdominal ultrasound or CT scan and chest radiography).
  • Patients in the adjuvant cohort have undergone R0-resection by total mesorectal excision (TME) of a pT3-4 Nany or Tany Npositive non-metastatic rectal cancer.
  • Patients treated in the neoadjuvant cohort need to have a clinical T3-4 Nany or Tany Npositive tumour staged by endoscopic ultrasound, provided the lower border of the tumour is located 0 - 16 cm from the anal verge measured by rigid rectoscopy and the primary tumour is deemed resectable by TME surgery on the basis of clinical assessment. Other eligibility criteria comprise: WHO status of zero or one; adequate liver, renal, and bone marrow function defined as follows: leucocyte count > 3,500/µl, thrombocyte count > 100,000/µl, hemoglobin > 10.0 g/dl; serum bilirubine < 2.0 mg/dl, serum creatinine < 2.0 mg/dl.

Exclusion criteria:

  • Prior treatment for rectal cancer, prior chemo- or immunotherapy, prior pelvic radiotherapy, or a history of other malignant diseases within the past five years with the exception of succesfully treated basal carcinoma of the skin or carcinoma in situ of the uterine cervix.
  • Participation in another trial, pregnancy, breast-feeding, unwillingness to use effective contraception, or a medical condition or concomitant illness which could potentially interfere with compliance to the protocol are regarded as exclusion criteria, as well.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01500993

Dr Martina Grunewald
Aschersleben, Germany
Dr Hans Walter Lindemann
Hagen, Germany
Prof Hartmut Link
Kaiserslautern, Germany
Dr Elisabeth Fritz
Koblenz, Germany
Dr Stephan Kremers
Lebach, Germany
Dr Lothar Müller
Leer, Germany
Dr Christain Constantin
Lemgo, Germany
Dr Erika Kettner
Magdeburg, Germany
Dr Markus Moehler
Mainz, Germany
Dr Udo Hieber
Mannheim, Germany
Prof Ralf Hofheinz
Mannheim, Germany
Dr Matthias Hipp
Regensburg, Germany
Prof Axel Matzdorff
Saarbrücken, Germany
Dr Stephan Laechelt
Tübingen, Germany
Sponsors and Collaborators
Universitätsmedizin Mannheim
Study Chair: Ralf Hofheinz, MD Universitätsmedizin Mannheim Germany, University of Heidelberg
Study Chair: Frederik Wenz, MD Universitätsmedizin Mannheim, Germany, University of Heidelberg
Study Chair: Stefan Post, MD Universitätsmedizin Mannheim, Germany, University of Heidelberg
Study Chair: Andreas Hochhaus, MD Universitätsklinikum Jena, Germany

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Frederik Wenz, Prof Dr med. F. Wenz, Universitätsmedizin Mannheim Identifier: NCT01500993     History of Changes
Other Study ID Numbers: Rektum III
First Posted: December 29, 2011    Key Record Dates
Last Update Posted: December 29, 2011
Last Verified: December 2011

Keywords provided by Frederik Wenz, Universitätsmedizin Mannheim:
Rectal cancer
phase-III trial

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