Clinical Trial Results:
A Single-Arm, Open Label Study of Aflibercept as Maintenance Therapy Following Induction with Aflibercept in Combination with XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient
Summary
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EudraCT number |
2013-000858-22 |
Trial protocol |
IT |
Global end of trial date |
23 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Apr 2016
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First version publication date |
06 Apr 2016
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Other versions |
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 |
AFLIBC06561
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01955629 | ||
WHO universal trial number (UTN) |
U1111-1143-3015 | ||
Other trial identifiers |
Study name: AMOR | ||
Sponsors
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Sponsor organisation name |
Sanofi Aventis Groupe (SAG)
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Sponsor organisation address |
54, rue La Boétie, Paris, France, 75008
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Public contact |
Trial Transparency Team, Sanofi Aventis Groupe (SAG), Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Groupe (SAG), Contact-US@sanofi.com
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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 |
Final
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Date of interim/final analysis |
13 May 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Mar 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Study Part 1: To determine the recommended dose for the aflibercept, oxaliplatin and capecitabine (XELOX) combination to be used in the Part 2 of the study. Study Part 2: To assess the percentage of subjects without progression of the disease at 6 months after the start of maintenance therapy with aflibercept single-agent, following the first-line induction therapy with XELOX and aflibercept combination in subjects with previously untreated metastatic colorectal cancer.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Dec 2013
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Long term follow-up planned |
No
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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 |
Italy: 4
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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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) |
0
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 2 sites in Italy. A total of 6 subjects were screened between 17 Dec 2013 and 24 Feb 2014, out of which 4 subjects were enrolled and treated. | ||||||
Pre-assignment
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Screening details |
Subjects enrolled in Part-1 of study to assess recommended phase 2 dose (RP2D) of combination of aflibercept with oxaliplatin and capecitabine. 3 subjects discontinued due to adverse events (AE) and 1 subject due to disease progression (DP) at dose level 1 of treatment. Part-2 of study (efficacy and safety evaluation) was not performed. | ||||||
Period 1
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Period 1 title |
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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Aflibercept + XELOX (Oxaliplatin and Capecitabine) | ||||||
Arm description |
Aflibercept in combination with Oxaliplatin and Capecitabine, up to 6 cycles as induction therapy, followed by aflibercept as maintenance therapy up to DP or unacceptable toxicity or subject's refusal of further treatment. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Aflibercept
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Investigational medicinal product code |
AVE0005
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Other name |
Zaltrap
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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 |
Aflibercept 6 mg/kg IV infusion (up to 2 hours) on Day 1 every 3 weeks (q3w).
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Investigational medicinal product name |
Oxaliplatin
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Investigational medicinal product code |
SR96669
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Other name |
Eloxatin
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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 |
Oxaliplatin 100 mg/m^2 IV infusion for 2 hours on Day 1 q3w.
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Investigational medicinal product name |
Capecitabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Capecitabine 850 mg/m^2 twice daily from Day 1 to Day 14 of each cycle of 3 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Aflibercept + XELOX (Oxaliplatin and Capecitabine)
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Reporting group description |
Aflibercept in combination with Oxaliplatin and Capecitabine, up to 6 cycles as induction therapy, followed by aflibercept as maintenance therapy up to DP or unacceptable toxicity or subject's refusal of further treatment. | |||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aflibercept + XELOX (Oxaliplatin and Capecitabine)
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Reporting group description |
Aflibercept in combination with Oxaliplatin and Capecitabine, up to 6 cycles as induction therapy, followed by aflibercept as maintenance therapy up to DP or unacceptable toxicity or subject's refusal of further treatment. |
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End point title |
Part 1:Number of Subjects With Dose Limiting Toxicities (DLTs) [1] | ||||||
End point description |
DLTs were assessed by National Cancer Institute Common Terminology Criteria for AEs version4.03 and were any of the AEs:G4 neutropenia lasting>7 days;febrile neutropenia or neutropenic infection;G4 thrombocytopenia;G3 thrombocytopenia with bleeding requiring transfusion;G4 non-hematological treatment related event;G3 nausea/vomiting/diarrhea lasting>/=4 days despite corrective measures;G3 non-hematological toxicities:anorexia,fatigue,hypertension only if G4 or not medically controlled and G3 peripheral sensory neuropathy not improved to G<2 at retreatment;urinary protein excretion of>3.5 gram per 24hours not recovered to<2.0 gram per 24hours within 2 weeks;symptomatic arterial thromboembolic events including cerebrovascular accidents,myocardial infarction,transient ischemic attacks, new onset/worsening of pre-existing angina.Evaluable DLT population was subset of whole part-1 subjects exposed to at least 1dose of treatment (even incomplete) and with evaluable DLT assessment at cycle1.
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End point type |
Primary
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End point timeframe |
Cycle 1 (Up to 3 weeks)
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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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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No statistical analyses for this end point |
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End point title |
Part 2: Number of Subjects With Progression Free Survival (PFS) at 6 Months After the Start of Maintenance Therapy [2] | ||||||
End point description |
It describes the number of subjects alive without progression at 6 months after the start of Aflibercept maintenance therapy. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Primary
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End point timeframe |
6 months after the start of maintenance therapy.
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Notes [2] - 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: Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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Notes [3] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 1: Number of Subjects With Tumor Responses (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Progressive Disease [PD]) | ||||||||||||||
End point description |
Tumor assessment was performed by Abdomino-Pelvic Computed Tomography Scan or Magnetic Resonance Imaging(MRI) and chest X-ray or chest CT-scan to assess disease status at baseline and every 9 weeks during study treatment up to DP. Target lesions evaluated using Response Evaluation Criteria In Solid Tumors(RECIST) version1.1, wherein CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter(LD) of target lesions taking as reference baseline sum LD; PD=20% increase in sum of LD of target lesions taking as reference smallest sum in study and SD=small changes not met above criteria. Evaluable Population(EP) for tumor response was subset of ITT population (all subjects who gave informed consent and successfully registered into study) with measurable disease at study entry,received at least 1 cycle of study treatment, with at least 1 post baseline tumor evaluation, except for early DP or death.
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End point type |
Secondary
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End point timeframe |
Baseline and every 9 weeks up to DP (up to 15 months).
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No statistical analyses for this end point |
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End point title |
Part 2: PFS | ||||||||
End point description |
PFS was defined as the time interval from the date of registration into the study to the date of first observation of disease progression or death (due to any cause), whichever was first. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
From the date of enrollment up to the date of DP or death, whichever occurred first (up to 15 months).
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Notes [4] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 2: Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time interval from the date of registration into the study to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the earliest between the last date the subject was known to be alive and the end of study date. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
From the date of enrollment up to the date of death (up to 15 months).
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Notes [5] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 2: Overall Rate of Resectability of Metastatic Lesions | ||||||||
End point description |
Overall metastases resection rate was defined as the percentage of subjects reaching an R0 metastases resection, defined as the complete absence of invasive carcinoma on histological examination at the time of definitive surgery (if performed). Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
12 months after the last subject enrolled.
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Notes [6] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 2: Number of Subjecs With CR or PR | ||||||
End point description |
Tumor assessment was performed by Abdomino-Pelvic Computed Tomography Scan or MRI and chest X-ray or chest CT-scan to assess the disease status at baseline and then every 9 weeks during study treatment up to DP. Target lesions were evaluated using RECIST version 1.1, wherein CR = disappearance of all target lesions; PR = 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
Baseline and every 9 weeks up to end of study completion (15 months).
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Notes [7] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 2: Pharmacodynamic Parameters: Modulation of Circulating Analytes | ||||||
End point description |
Blood and tumor samples were to be collected to evaluate the pharmacodynamic parameters including the assessment of the modulation of circulating analytes such as cytokines and angiogenic factors. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.
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Notes [8] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Part 2: Aflibercept Biomarkers Evaluation | ||||||
End point description |
Blood and tumor samples were to be collected to evaluate proteomic biomarkers such as factors and receptors related to angiogenesis process, inflammation, and tumor progression. Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed.
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End point type |
Secondary
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End point timeframe |
Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.
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Notes [9] - Due to premature recruitment discontinuation, none of the planned efficacy analysis was performed. |
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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 |
All AEs were collected from signature of the informed consent form up to 30 days after the last administration of treatment regardless of seriousness or relationship to study treatment.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (from the first study treatment administration to 30 days after the last study treatment administration).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Aflibercept + XELOX (Oxaliplatin and Capecitabine)
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Reporting group description |
Aflibercept in combination with Oxaliplatin and Capecitabine, up to 6 cycles as induction therapy, followed by aflibercept as maintenance therapy up to DP or unacceptable toxicity or subject's refusal of further treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
The study enrollment was prematurely halted due to safety reasons. |