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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Frederik Wenz, University Hospital Mannheim
ClinicalTrials.gov Identifier:
NCT01500993
First received: December 21, 2011
Last updated: December 26, 2011
Last verified: December 2011

December 21, 2011
December 26, 2011
March 2002
March 2011   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: 5-year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01500993 on ClinicalTrials.gov Archive Site
  • disease-free survival (DFS) [ Time Frame: 3-year DFS ] [ Designated as safety issue: Yes ]
  • Local recurrence rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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
Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. doi: 10.1016/S1470-2045(12)70116-X. Epub 2012 Apr 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
401
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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01500993
Rektum III
No
Frederik Wenz, University Hospital 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