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

Primary Purpose

Rectal Cancer

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Capecitabine
5-FU
Sponsored by
Universitätsmedizin Mannheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal cancer, Chemoradiotherapy, Capecitabine, phase-III trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Dr Martina Grunewald
  • Dr Hans Walter Lindemann
  • Prof Hartmut Link
  • Dr Elisabeth Fritz
  • Dr Stephan Kremers
  • Dr Lothar Müller
  • Dr Christain Constantin
  • Dr Erika Kettner
  • Dr Markus Moehler
  • Dr Udo Hieber
  • Prof Ralf Hofheinz
  • Dr Matthias Hipp
  • Prof Axel Matzdorff
  • Dr Stephan Laechelt

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

5-Fluorouracil (5-FU)

Capecitabine

Arm Description

Drug - 5FU based chemoradiotherapy and chemotherapy

Drug - Capecitabine-based radiochemotherapy and chemotherapy

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

disease-free survival (DFS)
Local recurrence rate
Percentage of patient with local recurrence

Full Information

First Posted
December 21, 2011
Last Updated
November 24, 2020
Sponsor
Universitätsmedizin Mannheim
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1. Study Identification

Unique Protocol Identification Number
NCT01500993
Brief Title
Capecitabine in the Perioperative Treatment of Rectal Cancer
Acronym
Rektum-III
Official Title
5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitätsmedizin Mannheim

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Rectal cancer, Chemoradiotherapy, Capecitabine, phase-III trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
401 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5-Fluorouracil (5-FU)
Arm Type
Active Comparator
Arm Description
Drug - 5FU based chemoradiotherapy and chemotherapy
Arm Title
Capecitabine
Arm Type
Experimental
Arm Description
Drug - Capecitabine-based radiochemotherapy and chemotherapy
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Intervention Name(s)
5-FU
Other Intervention Name(s)
5-Fluorouracil
Intervention Description
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)
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
5-year
Secondary Outcome Measure Information:
Title
disease-free survival (DFS)
Time Frame
3-year DFS
Title
Local recurrence rate
Description
Percentage of patient with local recurrence
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralf Hofheinz, MD
Organizational Affiliation
Universitätsmedizin Mannheim Germany, University of Heidelberg
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Frederik Wenz, MD
Organizational Affiliation
Universitätsmedizin Mannheim, Germany, University of Heidelberg
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Stefan Post, MD
Organizational Affiliation
Universitätsmedizin Mannheim, Germany, University of Heidelberg
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Andreas Hochhaus, MD
Organizational Affiliation
Universitätsklinikum Jena, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
Dr Martina Grunewald
City
Aschersleben
Country
Germany
Facility Name
Dr Hans Walter Lindemann
City
Hagen
Country
Germany
Facility Name
Prof Hartmut Link
City
Kaiserslautern
Country
Germany
Facility Name
Dr Elisabeth Fritz
City
Koblenz
Country
Germany
Facility Name
Dr Stephan Kremers
City
Lebach
Country
Germany
Facility Name
Dr Lothar Müller
City
Leer
Country
Germany
Facility Name
Dr Christain Constantin
City
Lemgo
Country
Germany
Facility Name
Dr Erika Kettner
City
Magdeburg
Country
Germany
Facility Name
Dr Markus Moehler
City
Mainz
Country
Germany
Facility Name
Dr Udo Hieber
City
Mannheim
Country
Germany
Facility Name
Prof Ralf Hofheinz
City
Mannheim
Country
Germany
Facility Name
Dr Matthias Hipp
City
Regensburg
Country
Germany
Facility Name
Prof Axel Matzdorff
City
Saarbrücken
Country
Germany
Facility Name
Dr Stephan Laechelt
City
Tübingen
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
22503032
Citation
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.
Results Reference
result
PubMed Identifier
25400468
Citation
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.
Results Reference
derived

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Capecitabine in the Perioperative Treatment of Rectal Cancer

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