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
  Purpose

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


Condition Intervention Phase
Rectal Cancer
Drug: Capecitabine
Drug: 5-FU
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial

Resource links provided by NLM:


Further study details as provided by Universitätsmedizin Mannheim:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 5-year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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


Enrollment: 401
Study Start Date: March 2002
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500993

Locations
Germany
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
Prof Ralf Hofheinz
Mannheim, Germany
Dr Udo Hieber
Mannheim, Germany
Dr Matthias Hipp
Regensburg, Germany
Prof Axel Matzdorff
Saarbrücken, Germany
Dr Stephan Laechelt
Tübingen, Germany
Sponsors and Collaborators
Universitätsmedizin Mannheim
Investigators
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
  More Information

No publications provided by Universitätsmedizin Mannheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Frederik Wenz, Prof Dr med. F. Wenz, University Hospital Mannheim
ClinicalTrials.gov Identifier: NCT01500993     History of Changes
Other Study ID Numbers: Rektum III
Study First Received: December 21, 2011
Last Updated: December 26, 2011
Health Authority: Germany: Ethics Commission

Keywords provided by Universitätsmedizin Mannheim:
Rectal cancer
Chemoradiotherapy
Capecitabine
phase-III trial

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

ClinicalTrials.gov processed this record on July 26, 2014