Capecitabine in the Perioperative Treatment of Rectal Cancer

NCT ID: NCT01500993

Last Updated: 2020-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 401 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-03-31
• Study Completion Date: 2011-03-31

Brief Summary

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

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.

Conditions

Rectal Cancer

Keywords

Rectal cancer; Chemoradiotherapy; Capecitabine; phase-III trial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5-Fluorouracil (5-FU)

Drug - 5FU based chemoradiotherapy and chemotherapy

Group Type: ACTIVE_COMPARATOR

5-FU

Intervention Type: DRUG

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)

Capecitabine

Drug - Capecitabine-based radiochemotherapy and chemotherapy

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Capecitabine standard therapy (i.e. 2,500 mg/sqm) x 5 cycles plus 1 cycle of capecitabine based chemoradiotherapy (1.650 mg/sqm)

Interventions

Capecitabine

Capecitabine standard therapy (i.e. 2,500 mg/sqm) x 5 cycles plus 1 cycle of capecitabine based chemoradiotherapy (1.650 mg/sqm)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Xeloda; 5-Fluorouracil

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsmedizin Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Frederik Wenz

Co-Investigator, Head Department of Radiation Oncology Mannheim

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ralf Hofheinz, MD

Role: STUDY_CHAIR

Universitätsmedizin Mannheim Germany, University of Heidelberg

Frederik Wenz, MD

Role: STUDY_CHAIR

Universitätsmedizin Mannheim, Germany, University of Heidelberg

Stefan Post, MD

Role: STUDY_CHAIR

Universitätsmedizin Mannheim, Germany, University of Heidelberg

Andreas Hochhaus, MD

Role: STUDY_CHAIR

Universitätsklinikum Jena, Germany

Locations

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

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 22503032 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25400468 (View on PubMed)

Other Identifiers

Rektum III

Identifier Type: -

Identifier Source: org_study_id