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5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial

Phase 3
18 Years
Not Enrolling
Rectal Cancer

Thank you

Trial Information

5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial

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.

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.

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Outcome Time Frame:


Safety Issue:


Principal Investigator

Ralf Hofheinz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Universitätsmedizin Mannheim Germany, University of Heidelberg


Germany: Ethics Commission

Study ID:

Rektum III



Start Date:

March 2002

Completion Date:

March 2011

Related Keywords:

  • Rectal Cancer
  • Rectal cancer
  • Chemoradiotherapy
  • Capecitabine
  • phase-III trial
  • Rectal Neoplasms