Rektum-III: Capecitabine in the Perioperative Treatment of Rectal Cancer

Sponsor

Universitätsmedizin Mannheim (Other)

Overall Status

Completed

CT.gov ID

NCT01500993

Collaborator

(none)

401

Enrollment

Locations

Arms

108

Duration (Months)

28.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Capecitabine Drug: 5-FU	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

401 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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 cycle 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 Names: 5-Fluorouracil
Experimental: Capecitabine Drug - Capecitabine-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 Names: Xeloda

Arm

Intervention/Treatment

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 cycle 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 Names:

5-Fluorouracil

Experimental: Capecitabine

Drug - Capecitabine-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 Names:

Xeloda

Outcome Measures

Primary Outcome Measures

Overall survival [5-year]

Secondary Outcome Measures

disease-free survival (DFS) [3-year DFS]
Local recurrence rate [5 years]
Percentage of patient with local recurrence

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 N any or T any N positive non-metastatic rectal cancer.
Patients treated in the neoadjuvant cohort need to have a clinical T3-4 N any or T any N positive 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 bilirubin < 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 successfully 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

Locations

	Site	City	Country
1	Dr Martina Grunewald	Aschersleben	Germany
2	Dr Hans Walter Lindemann	Hagen	Germany
3	Prof Hartmut Link	Kaiserslautern	Germany
4	Dr Elisabeth Fritz	Koblenz	Germany
5	Dr Stephan Kremers	Lebach	Germany
6	Dr Lothar Müller	Leer	Germany
7	Dr Christain Constantin	Lemgo	Germany
8	Dr Erika Kettner	Magdeburg	Germany
9	Dr Markus Moehler	Mainz	Germany
10	Dr Udo Hieber	Mannheim	Germany
11	Prof Ralf Hofheinz	Mannheim	Germany
12	Dr Matthias Hipp	Regensburg	Germany
13	Prof Axel Matzdorff	Saarbrücken	Germany
14	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