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

Tracking Information

• First Submitted Date: December 21, 2011
• First Posted Date: December 29, 2011
• Last Update Posted Date: November 27, 2020
• Study Start Date: March 2002
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 26, 2011): Overall survival [ Time Frame: 5-year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 26, 2011)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Capecitabine in the Perioperative Treatment of Rectal Cancer
• Official Title: 5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rectal Cancer

Intervention

• 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
• 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

Study Arms

• Active Comparator: 5-Fluorouracil (5-FU)
  Drug - 5FU based chemoradiotherapy and chemotherapy
  Intervention: Drug: 5-FU
• Experimental: Capecitabine
  Drug - Capecitabine-based radiochemotherapy and chemotherapy
  Intervention: Drug: Capecitabine

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 26, 2011): 401
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: March 2011
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01500993
• Other Study ID Numbers: Rektum III
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Frederik Wenz, Universitätsmedizin Mannheim
• Original Responsible Party: Frederik Wenz, Universitätsmedizin Mannheim, Prof Dr med. F. Wenz
• Current Study Sponsor: Universitätsmedizin Mannheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Universitätsmedizin Mannheim
• Verification Date: November 2020