Clinical Trial Results:
Preoperative combined radiochemotherapy for patients with newly diagnosed, primary operable and locally advanced rectal carcinoma (cT3, Nx, M0) of the lower and middle rectum
Summary
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EudraCT number |
2004-002358-72 |
Trial protocol |
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Global end of trial date |
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Results information
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Results version number |
v1 |
This version publication date |
10 Sep 2021
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First version publication date |
10 Sep 2021
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ABCSG R02 (95)/TAKO 05
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00297141 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
ABCSG (Austrian Breast & Colorectal Cancer Study Group)
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Sponsor organisation address |
Nußdorfer Platz 8/12, Vienna, Austria, 1190
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Public contact |
Hannes Fohler (Trial Office Director), ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at
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Scientific contact |
Prof. Dietmar Oefner-Velano, ABCSG (Austrian Breast & Colorectal Cancer Study Group), +43 14089230, info@abcsg.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
16 Nov 2006
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Nov 2006
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
Rate of T-downstaging (Reduction of the T-stadium) at the time of final surgery following the preoperative combined radiochemotherapy (chemotherapy: Oxaliplatin, Capecitabine)
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Protection of trial subjects |
A Data Monitoring Committee (DMC) was established to obtain Patient Safety. The responsibility of the DMC was to evaluate deviations of medical relevance and safety issues. The DMC decided on whether or not the patient should continue the study treatment due to safety issues. Major protocol deviations include all deviations endangering the basal medical concept of the study jeopardizing the safety of the patient. Minor protocol deviations include all other protocol deviations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Dec 2004
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
7 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 60
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Worldwide total number of subjects |
60
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EEA total number of subjects |
60
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
38
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 8 trial sites participated and had the possibility to recruit patients in this trial in Austria. A total of 60 patients were enrolled between Dec 2004 and Dec 2005. | ||||||||||
Pre-assignment
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Screening details |
Time period of max. 21 days for screening (from diagnosis to therapy start) in which inclusion and exclusion criteria were assessed and clinical laboratory tests were performed. | ||||||||||
Pre-assignment period milestones
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Number of subjects started |
60 | ||||||||||
Number of subjects completed |
60 | ||||||||||
Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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Combined radio chemotherapy | ||||||||||
Arm description |
Preoperative Chemoradiation with therapy start within 21 days after MRI. Radiotherapy: 5 x 5 days 1.8 Gy; total dose 45 Gy; Chemotherapy: Capecitabine 825mg/m² bid, on radiotherapy days (week 1-4), Oxaliplatin 50mg/m² iv., d 1, 8, 15, 22. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Xeloda
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Investigational medicinal product code |
RO 09-1978
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Other name |
Capecitabine
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
825 mg/m2/bid, on radiotherapy days (week 1-4)
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Investigational medicinal product name |
Eloxatin
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Investigational medicinal product code |
SR 96669
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Other name |
Oxaliplatin
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
50mg/m2 BSA per day (d1, d8, d15, d22)
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The intent-to-treat population (ITT) consisted of all patients who received at least one dose of study medication. All efficacy and safety analyses were performed on this population.
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End points reporting groups
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Reporting group title |
Combined radio chemotherapy
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Reporting group description |
Preoperative Chemoradiation with therapy start within 21 days after MRI. Radiotherapy: 5 x 5 days 1.8 Gy; total dose 45 Gy; Chemotherapy: Capecitabine 825mg/m² bid, on radiotherapy days (week 1-4), Oxaliplatin 50mg/m² iv., d 1, 8, 15, 22. | ||
Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The intent-to-treat population (ITT) consisted of all patients who received at least one dose of study medication. All efficacy and safety analyses were performed on this population.
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End point title |
Tumor down-categorization [1] | ||||||
End point description |
The primary efficacy variable was the rate of tumor down-categorization (defined as a decrease of ≥ 1 point(s)) at the T level. The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Primary
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Single arm study based on descriptive analysis only. |
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No statistical analyses for this end point |
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End point title |
Pathological Complete Response (pCR) | ||||||
End point description |
The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Other pre-specified
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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No statistical analyses for this end point |
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End point title |
Confirmed Pathological Complete Response (pCR) | ||||||
End point description |
The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Other pre-specified
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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No statistical analyses for this end point |
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End point title |
Tumor status | ||||||||||||||||
End point description |
The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Other pre-specified
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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No statistical analyses for this end point |
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End point title |
Nodal status | ||||||||||||
End point description |
The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Other pre-specified
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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No statistical analyses for this end point |
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End point title |
Metastasis | ||||||||||
End point description |
The extent of residual tumor in the resected specimen was classified according to the TNM staging system of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC). In case of a complete pathological response (pCR; i.e., ypT0ypN0M0), an independent pathologist re-evaluated the tumor tissue. All efficacy parameters were analyzed descriptively.
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End point type |
Other pre-specified
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End point timeframe |
At the time of final surgery following the preoperative combined radio chemotherapy (chemotherapy: Oxaliplatin, Capecitabine).
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From first administration of radiochemotherapy until surgery
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.1
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Reporting groups
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Reporting group title |
Combined radiochemotherapy
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Apr 2010 |
According to Protocol Amendment #1, collection of prolonged (after surgery) follow up survival data was done. This data should enable estimation of survival curves for overall survival, cancer specific survival and relapse-free survival. Additionally, relationship between study primary endpoints tumor stage downstaging and yPCR and survival endpoints was examined. It should be stated that study was not powered for comparison between chemotherapy response and survival endpoint. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Limitation of a nonrandomized design. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/21267531 |