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   44366   clinical trials with a EudraCT protocol, of which   7389   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:
    RAMTAS A Phase III study of RAMucirumab in combination with TAS102 vs. TAS102 monotherapy in chemotherapy refractory metastatic colorectal cancer patients

    Summary
    EudraCT number
    		 2017-004162-99
    Trial protocol
    		 DE  
    Global end of trial date
    30 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Nov 2025
    First version publication date
    07 Nov 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RAMTAS
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03520946
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 AIO number: AIO-KRK-0316/ass
    Sponsors
    Sponsor organisation name
    Frankfurter Institut für Klinische Krebsforschung IKF GmbH
    Sponsor organisation address
    Steinbacher Hohl 2-26, Frankfurt am Main, Germany,
    Public contact
    IKF GmbH, Frankfurter Institut für Klinische Krebsforschung IKF GmbH am , 0049 695899787-19, ramtas@ikf-khnw.de
    Scientific contact
    IKF GmbH, Frankfurter Institut für Klinische Krebsforschung IKF GmbH , 0049 695899787-19, ramtas@ikf-khnw.de
    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
    27 Aug 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of ramucirumab in combination with TAS102 (Trifluridin/Tipiracil-Lonsurf®) vs. TAS102 monotherapy in patients with refractory mCRC.
    Protection of trial subjects
    This clinical trial study was designed and shall be implemented and reported in accordance with the protocol, the AMG (Arzneimittelgesetz), the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC), and with the ethical principles laid down in the Declaration of Helsinki. The trial was authorized/Aapproved by the competent authority (Paul-Ehrlic-Institut, PEI) and the competent ethics committee responsible for the trial (“federführende Ethikkommission). Before recruitment into the clinical trial, each patient was informed That participant in the trial at any time without any declaration of reasons, which will lead to any disadvantage for the respective patient. The eligibility of a new patient was determined by the local investigator during regular visits. The examinatons for the study and the inclusion of the patient were done after detailed written and oral education about aims, methods, anticipated benefits and potential hazards of the study by use of the informed consent forms and after given written consent of the patient. Safety of Ramucircumab/TAS102 was monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported. An independent data safety and monitoring board (DSMB) was responsible for assessment of reports summarizing safety data or study results and gave recommendations for planned protocol amendments.
    Background therapy
    		 -
    Evidence for comparator
    		 TAS102 is a novel cytotoxic drug consisting of an antineoplastic nucleoside analogue (trifluridine; FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride; TPI). It is approved in Japan, the USA and Europe for the treatment of patients with mCRC who have been previously treated with, or are not candidates for fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy (if indicated). Ramucirumab is a human monoclonal antibody that specifically binds VEGF-R2. The binding of ramucirumab to VEGF-R2 prevents its interaction with the activating ligands VEGF-A, VEGF-C and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGFR-2, thereby inhibiting ligand-induced proliferation, downstream signaling components including ERK1/2, and migration of human endothelial cells. Ramucirumab was approved for as second line treatment of mCRC
    Actual start date of recruitment
    24 Jan 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 428
    Worldwide total number of subjects
    428
    EEA total number of subjects
    428
    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)
    248
    From 65 to 84 years
    175
    85 years and over
    5

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Between January 2019 and February 2023, 493 patients were screened for eligibility and 430 patients were randomized in 43 trial sites. 428 patients were included in the ITT population (213 in Arm A and 215 in Arm B).

    Pre-assignment
    Screening details
    		 Patients with refractory metastatic colorectal cancer (mCRC), who have progressed on/after, did not tolerate, refuse or have contraindications to fluoropyrimidines, oxaliplatin, irinotecan, anti-angiogenic therapies (bevacizumab, aflibercept, or regorafenib) and if indicated anti-EGFR antibodies (cetuximab or panitumumab)

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental Arm Ramu + TAS-102
    Arm description
    		 Patients received ramucirumab plus TAS-102 for a maximum of 6 cycles. (approx. 6 months), whereby TAS-102 was presicribed and administered within its label and according to clinical routin and thus represents Standard of Care (SOC) treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    SUB32795
    Other name
    Cyramza
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    8 mg/kg, i.v., on day 1 and day 15 of a 4-week cycle [Q4W])

    Investigational medicinal product name
    TAS-102
    Investigational medicinal product code
    Other name
    Trifluridine/tipiracil, Lonsurf
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    35 mg/m2, orally, twice a day on day 1 – 5 and day 8 – 12 of a 4-week cycle [Q4W]

    Arm title
    		 Control Arm TAS-102
    Arm description
    		 TAS-102 was prescibed and administered within its label and according to clinical routine orally, twice a day, on day 1-5 and 8-12 of a 4-week cycle and thus represents Standard of Care treatment
    Arm type
    		 Active comparator

    Investigational medicinal product name
    TAS-102
    Investigational medicinal product code
    Other name
    Trifluridine/tipiracil, Lonsurf
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    35 mg/m2, orally, twice a day on day 1 – 5 and day 8 – 12 of a 4-week cycle [Q4W]

    Number of subjects in period 1
    		Experimental Arm Ramu + TAS-102 Control Arm TAS-102
    Started
    213
    215
    Completed
    12
    5
    Not completed
    201
    210
         Physician decision
    12
    10
         Consent withdrawn by subject
    14
    16
         Toxicity
    11
    2
         Death
    22
    9
         Other
    7
    6
         Progressive disease
    135
    167

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Experimental Arm Ramu + TAS-102
    Reporting group description
    		 Patients received ramucirumab plus TAS-102 for a maximum of 6 cycles. (approx. 6 months), whereby TAS-102 was presicribed and administered within its label and according to clinical routin and thus represents Standard of Care (SOC) treatment.

    Reporting group title
    Control Arm TAS-102
    Reporting group description
    		 TAS-102 was prescibed and administered within its label and according to clinical routine orally, twice a day, on day 1-5 and 8-12 of a 4-week cycle and thus represents Standard of Care treatment

    Reporting group values
    		 Experimental Arm Ramu + TAS-102 Control Arm TAS-102 Total
    Number of subjects
    		 213 215 428
    Age categorical
    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)
    		 132 116 248
        From 65-84 years
    		 80 95 175
        85 years and over
    		 1 4 5
    Age continuous
    Units: years
        median (full range (min-max))
    		 61 (25 to 87) 63 (27 to 90) -
    Gender categorical
    Units: Subjects
        Female
    		 93 100 193
        Male
    		 120 115 235
    ECOG
    Units: Subjects
        ECOG 0
    		 116 110 226
        ECOG 1
    		 97 105 202
    Localization of primary tumor
    Units: Subjects
        Ascendens
    		 22 25 47
        Coecum
    		 27 20 47
        Descendens
    		 8 6 14
        Rectum
    		 87 69 156
        Sigma
    		 47 57 104
        Transversum
    		 8 22 30
        Other
    		 14 16 30
    Localization group
    Units: Subjects
        Right
    		 61 77 138
        Left
    		 149 138 287
        unknown
    		 3 0 3
    T stage
    Units: Subjects
        T1
    		 6 9 15
        T2
    		 10 10 20
        T3
    		 109 118 227
        T4
    		 63 57 120
        Tx
    		 25 21 46
    N stage
    Units: Subjects
        N0
    		 43 52 95
        N+
    		 169 162 331
        Missing
    		 1 1 2
    M stage
    Units: Subjects
        M0
    		 11 7 18
        M1
    		 202 208 410
    Histopathological grade
    Units: Subjects
        G1
    		 5 7 12
        G2
    		 140 149 289
        G3
    		 47 29 76
        unknown
    		 21 30 51
    No. of organs with metastases
    Units: Subjects
        1 organ
    		 37 61 98
        >1 organ
    		 165 147 312
        Unknown
    		 11 7 18
    Duration of previous anti-angiogenic therapies
    Units: Subjects
        < 12 months
    		 139 141 280
        > 12 months
    		 74 74 148
    RAS mutational status
    Units: Subjects
        Mutation
    		 133 131 264
        Wildtype
    		 80 84 164
    BRAF V600E mutational status
    Units: Subjects
        Mutation
    		 8 11 19
        Wildtype
    		 205 204 409

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental Arm Ramu + TAS-102
    Reporting group description
    		 Patients received ramucirumab plus TAS-102 for a maximum of 6 cycles. (approx. 6 months), whereby TAS-102 was presicribed and administered within its label and according to clinical routin and thus represents Standard of Care (SOC) treatment.

    Reporting group title
    Control Arm TAS-102
    Reporting group description
    		 TAS-102 was prescibed and administered within its label and according to clinical routine orally, twice a day, on day 1-5 and 8-12 of a 4-week cycle and thus represents Standard of Care treatment

    Subject analysis set title
    ITT Arm A
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intent-to-treat (ITT) population included all randomized patients. Treatment assignment was based on the randomized treatment (primary population). The ITT population is the primary population for the description of the patient and treatment characteristics and was used for the primary efficacy analysis.

    Subject analysis set title
    ITT Arm B
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The intent-to-treat (ITT) population included all randomized patients. Treatment assignment was based on the randomized treatment (primary population). The ITT population is the primary population for the description of the patient and treatment characteristics and was used for the primary efficacy analysis.

    Subject analysis set title
    PP Arm A
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This population included all randomized patients fulfilling the inclusion (except life expectancy of at least 3 months) and exclusion criteria and who received at least one cycle of the treatment. Treatment assignment was based on the treatment actually received.

    Subject analysis set title
    PP Arm B
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This population included all randomized patients fulfilling the inclusion (except life expectancy of at least 3 months) and exclusion criteria and who received at least one cycle of the treatment. Treatment assignment was based on the treatment actually received.

    Subject analysis set title
    Safety Analysis Set Arm A
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety set was used for all safety endpoints and comprised all patients randomized who received at least one dose of study treatment. Patients were analyzed according to the treatment actually received.

    Subject analysis set title
    Safety Analysis Set Arm B
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety set was used for all safety endpoints and comprised all patients randomized who received at least one dose of study treatment. Patients were analyzed according to the treatment actually received.

    Primary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival
    End point description
    End point type
    Primary
    End point timeframe
    time from randomization until death from any cause. If no event was observed (e.g., lost to follow-up) OS was censored at the day of last subject contact
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: months
    median (confidence interval 95%)
        Overall Survival
    7.5 (6.2 to 8.6)
    7.1 (6.0 to 8.3)
    7.5 (6.4 to 8.6)
    7.1 (6.1 to 8.4)
    Statistical analysis title
    		 Log Rank Test
    Comparison groups
    ITT Arm B v ITT Arm A
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2516
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Log Rank Test
    Comparison groups
    PP Arm A v PP Arm B
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2627
    Method
    		 Logrank
    Confidence interval

    Secondary: Progression free survival

    		 Close Top of page
    End point title
    		 Progression free survival
    End point description
    End point type
    Secondary
    End point timeframe
    time from randomization to the first occurrence of progression, as determined by the investigator using CT criteria, or death from any cause. If no event was observed (e.g., lost to follow-up) PFS was censored at the time of last tumor assessment.
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: months
    median (confidence interval 95%)
        PSF
    2.4 (2.1 to 3.0)
    2.1 (2.0 to 2.1)
    2.4 (2.07 to 2.96)
    2.1 (2.0 to 2.1)
    Statistical analysis title
    		 Log Rank Test
    Comparison groups
    ITT Arm A v ITT Arm B
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0035
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Log Rank Test
    Comparison groups
    PP Arm A v PP Arm B
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0047
    Method
    		 Logrank
    Confidence interval

    Secondary: OS rate 6 and 12 months

    		 Close Top of page
    End point title
    		 OS rate 6 and 12 months
    End point description
    End point type
    Secondary
    End point timeframe
    percentage of patients being alive 6 and 12 months, respectively, after randomization.
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: %
        OS@6
    59
    57
    60
    58
        OS@12
    31
    26
    31
    27
    No statistical analyses for this end point

    Secondary: Objective response rate

    		 Close Top of page
    End point title
    		 Objective response rate
    End point description
    End point type
    Secondary
    End point timeframe
    proportion of patients whose best overall response (BOR) from baseline was either a complete (CR) or partial response (PR) per RECIST 1.1 criteria.
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: %
        Objective response rate
    2
    2
    2
    2
    Statistical analysis title
    		 Fishers Exact Test
    Comparison groups
    ITT Arm A v ITT Arm B
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 1
    Method
    		 Fisher exact
    Confidence interval
    Statistical analysis title
    		 Fishers Exact Test
    Comparison groups
    PP Arm A v PP Arm B
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 1
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Disease control rate

    		 Close Top of page
    End point title
    		 Disease control rate
    End point description
    End point type
    Secondary
    End point timeframe
    proportion of patients with CR or PR or stable disease (SD) per RECIST 1.1 criteria.
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: %
        DCR
    40
    32
    41
    33
    Statistical analysis title
    		 Fischers Exact Test
    Comparison groups
    ITT Arm A v ITT Arm B
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0341
    Method
    		 Fisher exact
    Confidence interval
    Statistical analysis title
    		 Fischers Exact Test
    Comparison groups
    PP Arm A v PP Arm B
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0343
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Best overall response

    		 Close Top of page
    End point title
    		 Best overall response
    End point description
    End point type
    Secondary
    End point timeframe
    best overall response (BOR) from baseline per RECIST 1.1 criteria
    End point values
    		 ITT Arm A ITT Arm B PP Arm A PP Arm B
    Number of subjects analysed
    213
    215
    209
    209
    Units: Patients
        Complete response
    0
    0
    0
    0
        Partial response
    4
    4
    4
    4
        Stable disease
    81
    64
    81
    64
        Progressive disease
    94
    120
    94
    119
        Missing
    34
    27
    30
    22
    No statistical analyses for this end point

    Secondary: Efficay in patients with neutropenia

    		 Close Top of page
    End point title
    		 Efficay in patients with neutropenia
    End point description
    End point type
    Secondary
    End point timeframe
    ORR and DCR in patients who developed neutropenia grade ≥2 (ANC ≤1500/µl) in cycle 1
    End point values
    		 ITT Arm A ITT Arm B
    Number of subjects analysed
    52
    44
    Units: %
        ORR
    2
    0
        DCR
    40
    48
    No statistical analyses for this end point

    Secondary: Quality of Life @ 4 weeks

    		 Close Top of page
    End point title
    		 Quality of Life @ 4 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    Quality of life (QoL) was assessed every 4 weeks during therapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and the EuroQol 5 dimensions 5-level version (EQ-5D-5L). QoL response wa
    End point values
    		 ITT Arm A ITT Arm B
    Number of subjects analysed
    157
    162
    Units: patients
        Missing
    23
    11
        Deteriorated
    34
    43
        Stable
    78
    80
        Improved
    22
    28
    No statistical analyses for this end point

    Secondary: Quality of Life @ 8 weeks

    		 Close Top of page
    End point title
    		 Quality of Life @ 8 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    Quality of life (QoL) was assessed every 4 weeks during therapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and the EuroQol 5 dimensions 5-level version (EQ-5D-5L). QoL response wa
    End point values
    		 ITT Arm A ITT Arm B
    Number of subjects analysed
    157
    162
    Units: patients
        Missing
    53
    60
        Deteriorated
    44
    36
        Stable
    43
    44
        Improved
    17
    22
    No statistical analyses for this end point

    Secondary: Quality of Life @ 12 weeks

    		 Close Top of page
    End point title
    		 Quality of Life @ 12 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    Quality of life (QoL) was assessed every 4 weeks during therapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and the EuroQol 5 dimensions 5-level version (EQ-5D-5L).
    End point values
    		 ITT Arm A ITT Arm B
    Number of subjects analysed
    157
    162
    Units: patients
        Missing
    96
    119
        Deteriorated
    21
    14
        Stable
    30
    21
        Improved
    10
    8
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    after patient has given written informed consent until at least 30 days after the last dose of study treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Safety analysis set Arm A
    Reporting group description
    		 -

    Reporting group title
    Safety analysis set Arm B
    Reporting group description
    		 -

    Serious adverse events
    		 Safety analysis set Arm A Safety analysis set Arm B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    101 / 211 (47.87%)
    66 / 209 (31.58%)
         number of deaths (all causes)
    179
    186
         number of deaths resulting from adverse events
    20
    13
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    3 / 211 (1.42%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 211 (1.42%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboembolic event
         subjects affected / exposed
    3 / 211 (1.42%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death NOS
         subjects affected / exposed
    6 / 211 (2.84%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 6
    0 / 3
    Oedema limbs
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fever
         subjects affected / exposed
    2 / 211 (0.95%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pain
         subjects affected / exposed
    9 / 211 (4.27%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    9 / 211 (4.27%)
    7 / 209 (3.35%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 211 (0.95%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    2 / 211 (0.95%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    4 / 211 (1.90%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    heart failure
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    3 / 211 (1.42%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 211 (0.47%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 211 (0.95%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 211 (1.90%)
    5 / 209 (2.39%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    5 / 211 (2.37%)
    4 / 209 (1.91%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    colonic obstruction
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 211 (1.90%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    5 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal haemorrhage
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal obstruction
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal stenosis
         subjects affected / exposed
    0 / 211 (0.00%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    4 / 211 (1.90%)
    8 / 209 (3.83%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 211 (0.95%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 211 (0.95%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal perforation
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomach pain
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 211 (0.00%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites and bacterial peritonitis
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    2 / 211 (0.95%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 211 (1.42%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Haematuria
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle weakness left-sided
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (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
    Bronchial infection
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter related infection
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    3 / 211 (1.42%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peritoneal infection
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 211 (0.95%)
    3 / 209 (1.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Urinary tract infection
         subjects affected / exposed
    3 / 211 (1.42%)
    2 / 209 (0.96%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    unclear infection
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 211 (0.95%)
    0 / 209 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Safety analysis set Arm A Safety analysis set Arm B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    211 / 211 (100.00%)
    209 / 209 (100.00%)
    Investigations
    Alkaline phosphatase increased
         subjects affected / exposed
    11 / 211 (5.21%)
    9 / 209 (4.31%)
         occurrences all number
    13
    10
    Blood bilirubin increased
         subjects affected / exposed
    14 / 211 (6.64%)
    15 / 209 (7.18%)
         occurrences all number
    14
    19
    Neutrohil count decreased
         subjects affected / exposed
    99 / 211 (46.92%)
    84 / 209 (40.19%)
         occurrences all number
    174
    140
    Platelet count decreased
         subjects affected / exposed
    69 / 211 (32.70%)
    25 / 209 (11.96%)
         occurrences all number
    115
    41
    Weight loss
         subjects affected / exposed
    16 / 211 (7.58%)
    6 / 209 (2.87%)
         occurrences all number
    19
    6
    White blood cell count decreased
         subjects affected / exposed
    50 / 211 (23.70%)
    44 / 209 (21.05%)
         occurrences all number
    79
    62
    Vascular disorders
    Hypertension
         subjects affected / exposed
    56 / 211 (26.54%)
    12 / 209 (5.74%)
         occurrences all number
    78
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 211 (5.21%)
    3 / 209 (1.44%)
         occurrences all number
    12
    3
    Peripheral sensory neuropathy
         subjects affected / exposed
    10 / 211 (4.74%)
    11 / 209 (5.26%)
         occurrences all number
    13
    11
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    43 / 211 (20.38%)
    59 / 209 (28.23%)
         occurrences all number
    66
    68
    General disorders and administration site conditions
    Oedema limbs
         subjects affected / exposed
    25 / 211 (11.85%)
    9 / 209 (4.31%)
         occurrences all number
    28
    9
    Fatigue
         subjects affected / exposed
    72 / 211 (34.12%)
    62 / 209 (29.67%)
         occurrences all number
    83
    68
    Fever
         subjects affected / exposed
    14 / 211 (6.64%)
    7 / 209 (3.35%)
         occurrences all number
    14
    8
    Pain
         subjects affected / exposed
    30 / 211 (14.22%)
    30 / 209 (14.35%)
         occurrences all number
    36
    31
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    30 / 211 (14.22%)
    20 / 209 (9.57%)
         occurrences all number
    31
    22
    Ascites
         subjects affected / exposed
    16 / 211 (7.58%)
    7 / 209 (3.35%)
         occurrences all number
    19
    7
    Constipation
         subjects affected / exposed
    28 / 211 (13.27%)
    17 / 209 (8.13%)
         occurrences all number
    28
    18
    Diarrhoea
         subjects affected / exposed
    55 / 211 (26.07%)
    36 / 209 (17.22%)
         occurrences all number
    77
    44
    Mucositis oral
         subjects affected / exposed
    22 / 211 (10.43%)
    13 / 209 (6.22%)
         occurrences all number
    25
    13
    Nausea
         subjects affected / exposed
    72 / 211 (34.12%)
    53 / 209 (25.36%)
         occurrences all number
    98
    60
    Vomiting
         subjects affected / exposed
    43 / 211 (20.38%)
    29 / 209 (13.88%)
         occurrences all number
    57
    33
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    26 / 211 (12.32%)
    16 / 209 (7.66%)
         occurrences all number
    29
    16
    Epistaxis
         subjects affected / exposed
    14 / 211 (6.64%)
    1 / 209 (0.48%)
         occurrences all number
    15
    2
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    29 / 211 (13.74%)
    10 / 209 (4.78%)
         occurrences all number
    33
    11
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    12 / 211 (5.69%)
    7 / 209 (3.35%)
         occurrences all number
    13
    7
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    13 / 211 (6.16%)
    15 / 209 (7.18%)
         occurrences all number
    15
    16
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    23 / 211 (10.90%)
    17 / 209 (8.13%)
         occurrences all number
    24
    17

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Sep 2020
    Extansion to phase III study

    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
    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-Sat Dec 20 14:40:28 CET 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA