Clinical Trial Results:
ONCOFID-P (Paclitaxel-hyaluronic acid) in the intravesical therapy of patients with non-muscle invasive cancer of the bladder. A phase II marker lesion study
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Summary
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EudraCT number |
2009-012274-13 |
Trial protocol |
IT ES DE |
Global end of trial date |
30 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Aug 2022
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First version publication date |
09 Aug 2022
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Other versions |
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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 |
R39-09-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fidia Farmaceutici S.p.A
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Sponsor organisation address |
Via Ponte della Fabbrica 3/A, Abano Terme, Italy, 35031
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Public contact |
Nicola Giordan, Fidia Framaceutici, +39 0498232111, ngiordan@fidiapharma.it
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Scientific contact |
Nicola Giordan, Fidia Framaceutici, +39 0498232111, ngiordan@fidiapharma.it
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Sponsor organisation name |
Linical
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Sponsor organisation address |
Calle Las Norias 92, Madrid, Spain,
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Public contact |
Carlos M. Hortelano, Linical, +34 91 372 60 00,
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Scientific contact |
Carlos M. Hortelano, Linical, +34 91 372 60 00,
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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 |
27 Sep 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Oct 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess, at control visit (V8), the ablative activity of intravesical administration of Oncofid-P-B on a papillary marker tumor on patients suffering from multiple recurrent Ta G1-G2 papillary cancer of the bladder after 6 weeks of weekly study drug administration, through number and percentage of patients with Complete Response
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Protection of trial subjects |
The proced documentation of the study were designed to ensure that both the Sponsor and the Investigator strictly adhere to the ethical principles laid down in the current revision of the Declaration of Helsinki. The study was also carried out according both to the International Conference on Harmonisation Good Clinical Practice (ICH GCP) guidelines and local legal and regulatory requirements. Before being admitted to the study, the patient was fully informed of its nature, score and possible implications. The study was explained in a written form understandable to him/her, and the form signed by him/her. For incapacitated adults and patients under emergency situation and incapable to give consent, the written consent of the legally authorised representative was provided.
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Background therapy |
No other therapies were administered in the framework of the study. | ||
Evidence for comparator |
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Actual start date of recruitment |
17 May 2010
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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 |
Germany: 12
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Spain: 33
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Worldwide total number of subjects |
60
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EEA total number of subjects |
60
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
60
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
• Patients of both sexes aged > 18 years • Cytological or histological diagnosis of bladder cancer; • Multiple primary or recurrent Ta G1-G2 papillary cancer; • ECOG Performance Status 0 to 1; • Adequate bone marrow function: neutrophils ≥ 1.5 103/mL;platelet count ≥ 100 103/mm3; haemoglobin (hb) ≥ 10 g/dL • Written informed consent; | ||||||
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Period 1
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Period 1 title |
Oncofid-P-B 6W
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Oncofid-P-B | ||||||
Arm description |
A first treatment phase with a duration of 6 weeks | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Oncofid-P-B
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for intravesical solution
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Routes of administration |
Intravesical use
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Dosage and administration details |
The preparation of diluted solutions will be performed by the following steps:
- Take 40 mL of concentrate solution (see the table below);
- Pour the content in a 100 mL empty vial;
- Add 10 mL of glucosate solution;
- Mix the final solution;
- Administer the solution
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Period 2
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Period 2 title |
Oncofid-P-B 6+6 months
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Is this the baseline period? |
No | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
A second treatment maintenance phase with a treatment duration of 6+6 months (comprehensively 52 weeks)
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Arms
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Arm title
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Oncofid-P-B 6+6 | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Oncofid-P-B
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for intravesical solution
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Routes of administration |
Intravesical use
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Dosage and administration details |
The preparation of diluted solutions will be performed by the following steps:
- Take 40 mL of concentrate solution (see the table below);
- Pour the content in a 100 mL empty vial;
- Add 10 mL of glucosate solution;
- Mix the final solution;
- Administer the solution
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 60 patients completed the initial treatment period but only the patients that had a complete response at the end of this period (n=24) entered the maintenance period, |
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Baseline characteristics reporting groups
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Reporting group title |
Oncofid-P-B 6W
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety and efficacy analyses for the initial treatment phase will be conducted on all patients receiving at least one dose of the study drug.
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Subject analysis set title |
Per Protocol
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The PP will consist of all patients that received at least any amount of study drug and completed V8 without a major protocol deviation.
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End points reporting groups
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Reporting group title |
Oncofid-P-B
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Reporting group description |
A first treatment phase with a duration of 6 weeks | ||
Reporting group title |
Oncofid-P-B 6+6
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Reporting group description |
- | ||
Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety and efficacy analyses for the initial treatment phase will be conducted on all patients receiving at least one dose of the study drug.
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Subject analysis set title |
Per Protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP will consist of all patients that received at least any amount of study drug and completed V8 without a major protocol deviation.
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End point title |
Response rate at Visit 8-Safety Population [1] | ||||||||||
End point description |
Complete response was defined as complete disappearance of the marker lesion, as confirmed by negative post-treatment cystoscopy including a biopsy at the marker lesion site and the absence of new tumors at other site and negative cytology.
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End point type |
Primary
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End point timeframe |
Estimated at Visit 8, after 6 weeks of weekly study drug administration.
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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: No statistical analyses for this end point |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Response rate at Visit 8- Per Protocol [2] | ||||||||
End point description |
Complete response was defined as complete disappearance of the marker lesion, as confirmed by negative post-treatment cystoscopy including a biopsy at the marker lesion site and the absence of new tumors at other site and negative cytology.
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End point type |
Primary
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End point timeframe |
Estimated at Visit 8, after 6 weeks of weekly study drug administration.
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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: No statistical analyses for this end point |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number and percentage of patients with relapse within V22-Safety Population | ||||||||
End point description |
Regards to patients with relapse, defined as those patients who had no response, during the maintenance,
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End point type |
Secondary
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End point timeframe |
Patients with relapse within Visit 22.
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to relapse after Oncofid-P-B instillation-Safety Population | ||||||||
End point description |
Regards to patients with relapse, defined as those patients who had no response, during the maintenance.
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End point type |
Secondary
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End point timeframe |
During the maintenance period
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| No statistical analyses for this end point | |||||||||
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End point title |
Evaluate the safety profile of Oncofid-P-B-Safety Population | ||||||
End point description |
The secondary objectives were to determine the safety profile of Oncofid-P-B after the first administration and to assess tumor response.
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End point type |
Secondary
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End point timeframe |
During the 6 weeks instillation
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| No statistical analyses for this end point | |||||||
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End point title |
Evaluate the safety profile of Oncofid-P-B-Per Protocol | ||||||
End point description |
The secondary objectives were to determine the safety profile of Oncofid-P-B after the first administration and to assess tumor response.
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End point type |
Secondary
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End point timeframe |
During the 6 weeks instillation
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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 |
17 May 2010-04 November 2016
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
Oncofid-P-B
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Jul 2012 |
The decision to amend the protocol was made in light of the difficulties in identifying sufficient numbers of eligible participants, and in response to the growing need to effectively improve the patient recruitment.
The main changes to the protocol concern the inclusion/exclusion criteria. In particular, the study population was enlarged by the addition of patients with multiple primary Ta G1-G2 papillary cancer.
Additionally, it was decided to allow the participation of subjects:
- with a history of malignancies other than cancer of the upper urinary tract, cancer of the prostatic urethra and carcinoma in situ diagnosed more than 3 years before enrollment,
- with cardiovascular diseases that are not considered to be a contraindication for intravesical treatment.
We would underline that the above mentioned changes in the patient population will not in any way affect patients safety and security, and will not impact the study results or the risk/benefit ratio of the study, and that they were done in respect to the guidelines of the European Organization for Research and Treatment of Cancer (EORTC) and the Medical Research Council for lesion marker trials.
Other changes proposed in the present amendment are minor corrections of the protocol and the protocol synopsis, and the clarification with regard to some items as deemed necessary during the conduct of the study.
We attach herewith the detailed summary of changes for more information (“Comparative table protocol final version 02/version 03”, Version 1.0 dated 16 July 2012).
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
