Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43870   clinical trials with a EudraCT protocol, of which   7289   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Safety and Efficacy Study to Compare Capecitabine + Bevacizumab Versus Capecitabine, Concomitantly With Radiotherapy as Neoadjuvant Treatment for Patients With Localized and Resectable Rectal Cancer (AVAXEL)

    Summary
    EudraCT number
    		 2009-010192-24
    Trial protocol
    		 ES  
    Global end of trial date
    04 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jul 2020
    First version publication date
    16 Jul 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TTD-08-05
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01043484
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    TTD (Grupo de Tratamiento de los Tumores Digestivos)
    Sponsor organisation address
    C/ Téllez Nº 30 posterior 1º oficina 4.2 , MADRID, Spain, 28007
    Public contact
    TTD (Grupo de Tratamiento de los Tumores Digestivos), TTD (Grupo de Tratamiento de los Tumores Digestivos), +3491 3788275, ttd@ttdgroup.org
    Scientific contact
    TTD (Grupo de Tratamiento de los Tumores Digestivos), TTD (Grupo de Tratamiento de los Tumores Digestivos), +3491 3788275, ttd@ttdgroup.org
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Aug 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to evaluate the efficacy of neoadjuvant treatment with BVZ administered biweekly concomitantly with capecitabine and external RT measured as rate of complete pathological responses (RC p), and compare it with the rate of RC p obtained with capecitabine and external RT
    Protection of trial subjects
    In this trial safety and patient´s protection was an important objetive. Therefore, 3 intermediate safety analyzes were planned, after the first 6, 12 and 18 evaluable patients, in a dynamic way through direct feed back via e-mail or teleconference with researchers who had recruited these first patients without having to stop the recruitment or close the database in each of the 3 recruitment milestones. The possibility of two dose reductions of capecitabine depending on the toxicity observed was contemplated (725 and 625mg / m2) in the case that there were unacceptable toxicities in ≥ 33% ​​of patients at the initial doses or that have been reduced doses in more than 50% of patients. The doses of RT and bevacizumab were maintained unchanged. The security assessment was done on the safety population and was based mainly in the frequency and severity of adverse events abd serious adverse events. The use of any medication that patients needed for their correct clinical control was allowed, according to the criteria of the researcher, with the exception of those detailed in the protocol as forbidden. Data of all concomitant medication, as well as the diagnostic, therapeutic or surgical procedures performed during the study was required to be recorded in the eCRF.
    Background therapy
    		 differentUntil very recently, 5-Fluorouracil (5-FU) was the only systemic treatment effective to treat colorectal cancer but in the last five years, the incorporation into the therapeutic arsenal of new cytotoxics (capecitabine, irinotecan and oxaliplatin) and monoclonal antibodies against different targets (Cetuximab and Bevacizumab) have opened up new possibilities that have improved substantially the therapeutic results. In addition, the multidisciplinary treatment of rectal cancer has achieved an improvement both in the local and systemic control based on the recognition that the high incidence of local recurrences is due to the lack of sterility of the surgical radial margin, which led to the development of the total mesorectal resection (RTM) as a technique that achieves a substantial decrease in local recurrences, which is considered, at the present time, the standard surgical treatment for the medium and low rectal cancer. in addition, pelvic radiotherapy has also become an standard preoperative treatment in medium and low rectal cancer, based on its effect on the reduction of the tumor size and stage and the increase in the possibility of preservation of the anal sphincter in low tumors.
    Evidence for comparator
    		 In this trial, the comparator arm will inlcude bevacizumab as neoadjuvant treatment in combination with capecitabine and radiotherapy. In this sense, a preliminary phase II study conducted at the MDACC with the combination of RT + capecitabine (900 mg / m2 / 12 hours on RT days) and bevacizumab 5 mg / kg in rectal cancer has shown promising safety and efficacy, with 29% pCR in 17 patients.
    Actual start date of recruitment
    23 Dec 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 90
    Worldwide total number of subjects
    90
    EEA total number of subjects
    90
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    51
    From 65 to 84 years
    39
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Ninety patients were randomly assigned from December 2009 until March 2011 in 12 hospitals in Spain.

    Pre-assignment
    Screening details
    		 Patients >18y with locally advanced rectal adenocarcinoma, clinical stage II-III within <15 cm from the anal verge, and ECOG 0-1 were eligible. All patients were required to be candidates for definitive surgical resection and have adequate bone marrow and organ function and no previous chemotherapy or radiation for rectal cancer.

    Period 1
    Period 1 title
    OVERALL TRIAL (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinded trial.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A
    Arm description
    		 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent capecitabine 825 mg/m2 twice daily 5 days per week and bevacizumab 5 mg/kg once every 2 weeks as neoadjuvant treatment followed by surgery
    Arm type
    		 Experimental

    Investigational medicinal product name
    CAPECITABINE
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    825 mg/m2 twice daily 5 days per week

    Investigational medicinal product name
    BEVACIUMAB
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bevacizumab was given at the dose of 5 mg/kg once every 2 weeks (3 doses) as iv infusion.

    Investigational medicinal product name
    radiotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Radionuclide generator
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Radiotherapy was given during5 weeks of radiotherapy 45 Gy/25 fractions

    Arm title
    		 ARM B
    Arm description
    		 • Capecitabine: 825 mg/m2/12 h 5 days per week for 5 weeks. • Radiation therapy: 45 Gy (1.8 Gy per session, 5 days per week for 5 weeks)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    CAPECITABINE
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    • Capecitabine from ROCHE (Xeloda®) in film-coated tablets of 150 mg and 500 mg per tablet, at the dose of 825 mg/m2/12 h 5 days per week for 5 weeks.

    Investigational medicinal product name
    radiotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Radionuclide generator
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    • Radiation therapy: 45 Gy (1.8 Gy per session, 5 days per week for 5 weeks)

    Number of subjects in period 1
    		ARM A ARM B
    Started
    44
    46
    Completed
    41
    43
    Not completed
    3
    3
         Adverse event, non-fatal
    2
    3
         Non surgery
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent capecitabine 825 mg/m2 twice daily 5 days per week and bevacizumab 5 mg/kg once every 2 weeks as neoadjuvant treatment followed by surgery

    Reporting group title
    ARM B
    Reporting group description
    		 • Capecitabine: 825 mg/m2/12 h 5 days per week for 5 weeks. • Radiation therapy: 45 Gy (1.8 Gy per session, 5 days per week for 5 weeks)

    Reporting group values
    		 ARM A ARM B Total
    Number of subjects
    		 44 46 90
    Age categorical
    Subjects were between 37 and 78 years old.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 23 28 51
        From 65-84 years
    		 21 18 39
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        log mean (standard deviation)
    		 62.80 ( 9.99 ) 61.17 ( 10.55 ) -
    Gender categorical
    Units: Subjects
        Female
    		 19 16 35
        Male
    		 25 30 55
    ECOG
    Units: Subjects
        ECOG 0
    		 22 30 52
        ECOG 1
    		 22 16 38
    PRIMARY TUMOR LOCATION
    Units: Subjects
        UPPER THIRD
    		 10 10 20
        MIDDLE THIRD
    		 14 19 33
        LOWER THIRD
    		 20 16 36
        ND
    		 0 1 1
    TNM (T)
    Units: Subjects
        T3
    		 33 38 71
        T4
    		 10 7 17
        T2
    		 1 1 2
    TNM (N9
    Units: Subjects
        N0
    		 7 5 12
        N1
    		 18 27 45
        N2
    		 19 14 33
    TNM (M)
    Units: Subjects
        M0
    		 43 43 86
        MX
    		 1 3 4
    HISTOLOGIC SUBTYPE
    Units: Subjects
        ADENOCARCINOMA NOS
    		 38 44 82
        MUCINOUS ADENOCARCINOMA
    		 1 1 2
        OTHER
    		 5 1 6
    HISTOLOGICAL GRADE
    Units: Subjects
        GX
    		 13 17 30
        G1
    		 7 11 18
        G2
    		 20 16 36
        G3
    		 4 2 6
    TIME FROM DIAGNOSIS
    Units: YEEARS
        log mean (standard deviation)
    		 1.13 ( 0.51 ) 1.07 ( 0.51 ) -
    DISTANCE TO THE ANAL VERGE
    Units: CM
        log mean (standard deviation)
    		 6.74 ( 3.78 ) 6.75 ( 3.40 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ARM A
    Reporting group description
    		 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent capecitabine 825 mg/m2 twice daily 5 days per week and bevacizumab 5 mg/kg once every 2 weeks as neoadjuvant treatment followed by surgery

    Reporting group title
    ARM B
    Reporting group description
    		 • Capecitabine: 825 mg/m2/12 h 5 days per week for 5 weeks. • Radiation therapy: 45 Gy (1.8 Gy per session, 5 days per week for 5 weeks)

    Primary: PATHOLOGICAL COMPLETE RESPONSE-ITT POPULATION

    		 Close Top of page
    End point title
    		 PATHOLOGICAL COMPLETE RESPONSE-ITT POPULATION
    End point description
    Defined as ypT y el ypN = T0 y N0, it meaans, absence of tumoral cells in the surgical sample.
    End point type
    Primary
    End point timeframe
    OVERALL STUDY
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    44
    46
    Units: SUBJECTS
        Pathological complete response
    7
    5
        No pathological complete response
    36
    41
        Missing
    1
    0
    Statistical analysis title
    		 PRIMARY OBJECTIVE: PATHOLOGICAL COMPLETE RESPONSE
    Statistical analysis description
    ITT POPULATION
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5424
    Method
    		 Fisher exact
    Confidence interval

    Secondary: TUMORAL REGRESSION RATE- ITT POPULATION

    		 Close Top of page
    End point title
    		 TUMORAL REGRESSION RATE- ITT POPULATION
    End point description
    Degree of tumor regression has 5 categories, DRT 1 is complete pathological response; DRT 5 is disease progression.
    End point type
    Secondary
    End point timeframe
    OVERALL STUDY
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    44
    46
    Units: Subjects
        DTR 1
    8
    5
        DTR 2
    8
    15
        DTR 3
    14
    19
        DTR 4
    12
    6
        DTR 5
    0
    1
        ND
    1
    0
        Missing
    1
    0
    Statistical analysis title
    		 Pathologic response
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.1458
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Local relapse-free survival

    		 Close Top of page
    End point title
    		 Local relapse-free survival
    End point description
    Local relapse-free survival at 3 and 5 years was defined as the time between subject randomization and the first local relapse. Patients were censored if no local relapse was observed and the date of censorship used was the date of last contact.
    End point type
    Secondary
    End point timeframe
    At 3 and 5 years after randomization
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    44
    46
    Units: Subjects
        Yes
    0
    1
        No
    44
    45
    Statistical analysis title
    		 ITT population
    Statistical analysis description
    Local relapse-free survival at 3 and 5 years was the same value
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 1
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Distant relapse free surival rate

    		 Close Top of page
    End point title
    		 Distant relapse free surival rate
    End point description
    Distant relapse-free survival at 3 and 5 years was defined as the time between randomization of a subject and the presence of the first distant relapse. A subject was censored if no relapse was observed and the date of censorship used was the date of last contact.
    End point type
    Secondary
    End point timeframe
    At 3 and 5 years post-randomization.
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    44
    46
    Units: Subjects
        Yes
    11
    10
        No
    33
    36
    Statistical analysis title
    		 ITT population
    Statistical analysis description
    There were no significant differences at 3 and 5 years, therefore only the global results are posted
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.7147
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Overal survival rate at 3 and 5 years

    		 Close Top of page
    End point title
    		 Overal survival rate at 3 and 5 years
    End point description
    End point type
    Secondary
    End point timeframe
    At 3 and 5 years post-randomization.
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    44
    46
    Units: Subjects
        Dead
    10
    7
        Alive
    34
    39
    Statistical analysis title
    		 ITT population
    Comparison groups
    ARM B v ARM A
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.3629
    Method
    		 Chi-squared
    Confidence interval

    Secondary: To determine the percentage of R0 resections-PP population

    		 Close Top of page
    End point title
    		 To determine the percentage of R0 resections-PP population
    End point description
    R0 means complete resection
    End point type
    Secondary
    End point timeframe
    After surgery
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        R0
    39
    41
        R1
    1
    2
    Statistical analysis title
    		 Percentage of R0 resections
    Statistical analysis description
    PP population
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 1
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Rate of local relapse-PP population

    		 Close Top of page
    End point title
    		 Rate of local relapse-PP population
    End point description
    End point type
    Secondary
    End point timeframe
    Rate of local relapse at 3 and 5 years
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        Yes
    0
    1
        No
    40
    42
    Statistical analysis title
    		 Local relapse-free survival rate.
    Statistical analysis description
    PP population
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 1
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Rate of distant relapse-PP population

    		 Close Top of page
    End point title
    		 Rate of distant relapse-PP population
    End point description
    End point type
    Secondary
    End point timeframe
    Rate of distant relapse at 3 and 5 years
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        yes
    11
    9
        No
    29
    34
    Statistical analysis title
    		 Distant relapse-free survival rate.
    Statistical analysis description
    PP population
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.4844
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Rate of surgical complications-PP population

    		 Close Top of page
    End point title
    		 Rate of surgical complications-PP population
    End point description
    End point type
    Secondary
    End point timeframe
    Post-operatory complications
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: subjects
        Yes
    18
    17
        No
    22
    26
    Statistical analysis title
    		 Rate of surgical complications
    Statistical analysis description
    PP population
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.6144
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Rate of sphincter preservation-PP population

    		 Close Top of page
    End point title
    		 Rate of sphincter preservation-PP population
    End point description
    End point type
    Secondary
    End point timeframe
    Following CT-RT
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        Yes
    25
    28
        No
    15
    15
    Statistical analysis title
    		 Rate of sphincter preservation
    Statistical analysis description
    PP population
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.8043
    Method
    		 Chi-squared
    Confidence interval

    Secondary: T downstaging

    		 Close Top of page
    End point title
    		 T downstaging
    End point description
    End point type
    Secondary
    End point timeframe
    Following treatment
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: subbjects
        Improved
    23
    17
        No changes
    16
    26
        Worsened
    1
    0
    Statistical analysis title
    		 T downstaging
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.0979
    Method
    		 Fisher exact
    Confidence interval

    Secondary: N downstaging

    		 Close Top of page
    End point title
    		 N downstaging
    End point description
    End point type
    Secondary
    End point timeframe
    Following treatment
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        Improved
    23
    33
        No changes
    13
    8
        Worsened
    4
    1
        Non/evaluable
    0
    1
    Statistical analysis title
    		 N downstaging
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.1127
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Improvement in ypT and ypN

    		 Close Top of page
    End point title
    		 Improvement in ypT and ypN
    End point description
    End point type
    Secondary
    End point timeframe
    Following treatment
    End point values
    		 ARM A ARM B
    Number of subjects analysed
    40
    43
    Units: Subjects
        Improvement in both
    17
    15
        Improvement in one
    12
    19
        No improvement
    11
    8
        Non/evaluable
    0
    1
    Statistical analysis title
    		 Improvement in ypT and ypN
    Comparison groups
    ARM A v ARM B
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.3635
    Method
    		 Fisher exact
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs manifested up to 28 days after the last dose of study medications. Serious and not serious AEs related to study treatment up to 6 months after the last dose of study treatment.• AEs related to the administration of RT and were manifested by the (cont)
    Adverse event reporting additional description
    (cont)patients and/or that appeared in the control tests and were attributable to this procedure. • Possible surgical complications occurring either at the execution of the surgical resection of the tumor or those occurring within the first 30 days following the procedure.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 -

    Reporting group title
    Arm B
    Reporting group description
    		 -

    Serious adverse events
    		 Arm A Arm B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 44 (29.55%)
    11 / 46 (23.91%)
         number of deaths (all causes)
    10
    7
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer of the larynx
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomosis dehiscence
         subjects affected / exposed
    4 / 44 (9.09%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Pre-sacral hematoma
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal fistula
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticular perforation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bowel occlusion
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal hemorrhage
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    paralytic ileus
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Kidney failure
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fistula
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hemorrhagic intestinal diverticulitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Purulent exudate
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A Arm B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 44 (97.73%)
    44 / 46 (95.65%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 46 (6.52%)
         occurrences all number
    3
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    27 / 44 (61.36%)
    12 / 46 (26.09%)
         occurrences all number
    27
    12
    Pain
         subjects affected / exposed
    6 / 44 (13.64%)
    3 / 46 (6.52%)
         occurrences all number
    6
    3
    Pyrexia
         subjects affected / exposed
    4 / 44 (9.09%)
    4 / 46 (8.70%)
         occurrences all number
    4
    4
    Inflammation of the mucosa
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 46 (4.35%)
         occurrences all number
    4
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 44 (13.64%)
    6 / 46 (13.04%)
         occurrences all number
    6
    6
    Neutropenia
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 46 (4.35%)
         occurrences all number
    4
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    17 / 44 (38.64%)
    21 / 46 (45.65%)
         occurrences all number
    17
    21
    Rectal tenesmus
         subjects affected / exposed
    13 / 44 (29.55%)
    15 / 46 (32.61%)
         occurrences all number
    13
    15
    Rectal haemorrhage
         subjects affected / exposed
    10 / 44 (22.73%)
    13 / 46 (28.26%)
         occurrences all number
    11
    13
    Proctalgia
         subjects affected / exposed
    7 / 44 (15.91%)
    10 / 46 (21.74%)
         occurrences all number
    7
    10
    Nausea
         subjects affected / exposed
    7 / 44 (15.91%)
    5 / 46 (10.87%)
         occurrences all number
    7
    5
    Abdominal pain
         subjects affected / exposed
    7 / 44 (15.91%)
    5 / 46 (10.87%)
         occurrences all number
    7
    5
    Vomiting
         subjects affected / exposed
    7 / 44 (15.91%)
    4 / 46 (8.70%)
         occurrences all number
    7
    4
    Anorectal discomfort
         subjects affected / exposed
    5 / 44 (11.36%)
    5 / 46 (10.87%)
         occurrences all number
    5
    5
    Proctitis
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 46 (6.52%)
         occurrences all number
    3
    3
    Constipation
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 46 (4.35%)
         occurrences all number
    3
    2
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    6 / 44 (13.64%)
    3 / 46 (6.52%)
         occurrences all number
    6
    3
    Rash
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 46 (6.52%)
         occurrences all number
    3
    3
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    10 / 44 (22.73%)
    15 / 46 (32.61%)
         occurrences all number
    10
    15
    Urinary frequency
         subjects affected / exposed
    5 / 44 (11.36%)
    2 / 46 (4.35%)
         occurrences all number
    5
    2
    Hematuria
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 46 (4.35%)
         occurrences all number
    3
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 46 (6.52%)
         occurrences all number
    2
    3
    Infections and infestations
    Cystitis
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 46 (4.35%)
         occurrences all number
    4
    2
    Metabolism and nutrition disorders
    Loss of appetite
         subjects affected / exposed
    7 / 44 (15.91%)
    6 / 46 (13.04%)
         occurrences all number
    7
    6

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2009
    Treatment with oxaliplatin was eliminated after data presented on ASCO 2009. Minor mistakes correction. Protocol v 3.0 was generated
    19 Apr 2010
    Clarifications about RT treatment, management of toxicities and addition of a 4th sample for the sub study. Typos eliminated. Change of PI in H. de Valdecilla. Protocol v 4.0 was generated.
    20 Oct 2010
    Informative amendment, correcting inclusion criteria 5 and referring to Avastin’s IB (previously: technical datasheet). Protocol v 4.1 was generated.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/25886378
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 01 09:21:36 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA