Capecitabine in the Perioperative Treatment of Rectal Cancer (Rektum-III)
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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 |
- Overall survival [ Time Frame: 5-year ] [ Designated as safety issue: No ]
- 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 |
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| 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 | |
| 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 University Hospital 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 University Hospital 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 May 21, 2013