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

• ClinicalTrials.gov Identifier: NCT01500993
• Recruitment Status: Completed
• First Posted: December 29, 2011
• Last Update Posted: November 27, 2020
• Sponsor: Universitätsmedizin Mannheim
• Information provided by (Responsible Party): Frederik Wenz, Universitätsmedizin Mannheim

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 (Clinical Trial)
• 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: March 2002
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 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 Name: 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 Name: Xeloda

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 5-year ]

Secondary Outcome Measures :

1. disease-free survival (DFS) [ Time Frame: 3-year DFS ]
2. Local recurrence rate [ Time Frame: 5 years ]
   Percentage of patient with local recurrence

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 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

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

Dr Udo Hieber

Mannheim, Germany

Prof Ralf Hofheinz

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

Publications of Results:

Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Muller 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Garcia-Albeniz X, Gallego R, Hofheinz RD, Fernandez-Esparrach G, Ayuso-Colella JR, Bombi JA, Conill C, Cuatrecasas M, Delgado S, Gines A, Miquel R, Pages M, Pineda E, Pereira V, Sosa A, Reig O, Victoria I, Feliz L, Maria de Lacy A, Castells A, Burkholder I, Hochhaus A, Maurel J. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation. World J Gastroenterol. 2014 Nov 14;20(42):15820-9. doi: 10.3748/wjg.v20.i42.15820.

• Responsible Party: Frederik Wenz, Co-Investigator, Head Department of Radiation Oncology Mannheim, Universitätsmedizin Mannheim
• ClinicalTrials.gov Identifier: NCT01500993
• Other Study ID Numbers: Rektum III
• First Posted: December 29, 2011
• Last Update Posted: November 27, 2020
• Last Verified: November 2020

Keywords provided by Frederik Wenz, 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; Capecitabine; Fluorouracil; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs