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

December 21, 2011
December 29, 2011
December 29, 2011
March 2002
March 2011   (Final data collection date for primary outcome measure)
Overall survival [ Time Frame: 5-year ]
Same as current
No Changes Posted
  • disease-free survival (DFS) [ Time Frame: 3-year DFS ]
  • Local recurrence rate [ Time Frame: 5 years ]
    Percentage of patient with local recurrence
Same as current
Not Provided
Not Provided
Capecitabine in the Perioperative Treatment of Rectal Cancer
5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial
This study compares capecitabine with standard 5-FU in the perioperative treament of locally advanced rectal cancer.

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.

Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Rectal Cancer
  • 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
  • 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
  • Active Comparator: 5-Fluorouracil (5-FU)
    Drug - 5FU based chemoradiotherapy and chemotherapy
    Intervention: Drug: 5-FU
  • Experimental: Capecitabine
    Drug - Capecitabin-based radiochemotherapy and chemotherapy
    Intervention: Drug: Capecitabine

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
March 2011
March 2011   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Rektum III
Not Provided
Not Provided
Frederik Wenz, Universitätsmedizin Mannheim
Universitätsmedizin Mannheim
Not Provided
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
Universitätsmedizin Mannheim
December 2011

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