Clinical Trial Results:
A Single-Arm Phase II Clinical Study Of The Combination Of Carboplatin And Weekly Paclitaxel Plus Bevacizumab As First-Line Treatment In Patients With Epithelial Ovarian Cancer
Due to a system error, the data reported in v1 is not correct and has been removed from public view.
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Summary
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EudraCT number |
2008-008336-85 |
Trial protocol |
FR NL GB SE IT |
Global end of trial date |
29 Jul 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
29 Jul 2016
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First version publication date |
07 Aug 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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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 |
MO22225
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00937560 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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 |
29 Jul 2013
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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 |
29 Jul 2013
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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 |
The aim of this single arm study was to evaluate the efficacy and safety of first-line chemotherapy with carboplatin and dose-dense weekly paclitaxel plus bevacizumab (Avastin) in participants with epithelial ovarian, fallopian tube, or primary peritoneal cancer. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response (OR), duration of response (DR), overall survival (OS) at 1 and 2 years, biological progression-free interval (BPFI), and adverse events and safety assessments.
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Protection of trial subjects |
This study was conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the participant. This study fully adhered to the principles outlined in “Guideline for Good Clinical Practice” (GCP) International Conference on Harmonization (ICH) Tripartite Guideline (January 1997), or with local law if it afforded greater protection to the participant. For studies conducted in the European/ European Economic Area (EU/EEA) countries, investigators ensured compliance with the European (EU) Clinical Trial Directive (2001/20/EC).
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jun 2009
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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 |
Brazil: 7
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Country: Number of subjects enrolled |
France: 25
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Country: Number of subjects enrolled |
Italy: 21
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Country: Number of subjects enrolled |
Netherlands: 4
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Country: Number of subjects enrolled |
Norway: 8
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Country: Number of subjects enrolled |
Russian Federation: 50
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Country: Number of subjects enrolled |
Spain: 48
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Country: Number of subjects enrolled |
Sweden: 22
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Country: Number of subjects enrolled |
United Kingdom: 4
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Worldwide total number of subjects |
189
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EEA total number of subjects |
132
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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) |
152
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From 65 to 84 years |
37
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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 |
Potential participants were screened from 55 centers in Brazil, France, Italy, The Netherlands, Norway, Russia, Spain, Sweden, and the United Kingdom. One of the 190 enrolled participants withdrew consent before receiving treatment and was therefore not included in the analyzed Intent-to-treat (ITT) population of 189 participants. | ||||||||||||||||||
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Period 1
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Period 1 title |
Initial Treatment Phase
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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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Bevacizumab + Paclitaxel + Carboplatin | ||||||||||||||||||
Arm description |
Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of each 3-week cycle for a maximum of 17 cycles. Participants also received paclitaxel (80 milligrams per square meter [mg/m^2] IV) on Days 1, 8, and 15 and carboplatin IV (area under the curve of 6) on Day 1 of each 3-week cycle for a maximum of 8 cycles. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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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 |
Participants received bevacizumab 7.5 mg/kg IV on Day 1 of each 3-week cycle for a maximum of 17 cycles.
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Period 2
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Period 2 title |
Maintenance Phase
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Is this the baseline period? |
No | ||||||||||||||||||
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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Bevacizumab + Paclitaxel + Carboplatin | ||||||||||||||||||
Arm description |
Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of each 3-week cycle for a maximum of 17 cycles. Participants also received paclitaxel (80 milligrams per square meter [mg/m^2] IV) on Days 1, 8, and 15 and carboplatin IV (area under the curve of 6) on Day 1 of each 3-week cycle for a maximum of 8 cycles. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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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 |
Participants received bevacizumab 7.5 mg/kg IV on Day 1 of each 3-week cycle for a maximum of 17 cycles.
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Baseline characteristics reporting groups
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Reporting group title |
Initial Treatment Phase
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bevacizumab + Paclitaxel + Carboplatin
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Reporting group description |
Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of each 3-week cycle for a maximum of 17 cycles. Participants also received paclitaxel (80 milligrams per square meter [mg/m^2] IV) on Days 1, 8, and 15 and carboplatin IV (area under the curve of 6) on Day 1 of each 3-week cycle for a maximum of 8 cycles. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). | ||
Reporting group title |
Bevacizumab + Paclitaxel + Carboplatin
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Reporting group description |
Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of each 3-week cycle for a maximum of 17 cycles. Participants also received paclitaxel (80 milligrams per square meter [mg/m^2] IV) on Days 1, 8, and 15 and carboplatin IV (area under the curve of 6) on Day 1 of each 3-week cycle for a maximum of 8 cycles. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). | ||
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End point title |
Progression-free Survival [1] | ||||||||
End point description |
Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause, whichever occurred first. This analysis included the ITT population defined as all enrolled participants who received at least one dose of any study medication (carboplatin or paclitaxel or bevacizumab).
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End point type |
Primary
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End point timeframe |
Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
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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: This was a single arm treatment group study, therefore, a statistical analysis of the primary end point was not completed. |
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End point title |
Percentage of Participants With an Objective Response | ||||||||||||||
End point description |
An objective response was defined as either a complete response (CR) or a partial response (PR). Using RECIST, a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of greater than or equal to (≥)1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a baseline ovarian cancer mucin CA-125 level ≥2 times the upper limit of normal (ULN) who had a ≥50% reduction of CA-125 from baseline were included in the analysis according to CA-125 level.
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End point type |
Secondary
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End point timeframe |
Baseline, CA-125: every treatment visit before study drug administration, 30 days after last dose, and every 3 months; RECIST: at end of 3rd and 6th cycles, at Months 9 and 12, and every 6 months until end of study (up to a maximum of 36 months)
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| Notes [2] - ITT Population; n=number of participants analyzed for the referenced parameter. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Duration of Response | ||||||||||||||
End point description |
Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions, or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a baseline ovarian cancer mucin CA-125 level ≥ 2 times the ULN who had a ≥ 50% reduction of CA-125 from baseline were included in the analysis according to CA-125 level.
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End point type |
Secondary
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End point timeframe |
Baseline, CA-125: every treatment visit before study drug administration, 30 days after last dose, and every 3 months; RECIST: at end of 3rd and 6th cycles, at Months 9 and 12, and every 6 months until end of study (up to a maximum of 36 months)
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| Notes [3] - ITT Population; n=number of participants analyzed for the referenced parameter. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Overall Survival at 1 Year and 2 Years | ||||||||||||
End point description |
Time to death by any cause.
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End point type |
Secondary
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End point timeframe |
Year 1 and Year 2
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| Notes [4] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Biological Progression-free Interval (BPFI) | ||||||||
End point description |
BPFI defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. Precisely it is the first documented increase in CA-125 levels as follows: (1) CA-125 ≥2 times the ULN on 2 occasions at least 1 week apart (CA-125 within normal range pre-treatment) or (2) CA-125 ≥2 times the ULN on 2 occasions at least 1 week apart (elevated CA-125 pre-treatment and initial normalization of CA-125 on-treatment) or (3) CA-125 ≥2 times the nadir value, which is the lowest observed CA-125 value per participant on 2 occasions at least 1 week apart (elevated CA-125 pre-treatment which never normalized). 9999=median and 95% confidence interval was not reached as greater than 80% of participants were censored.
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End point type |
Secondary
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End point timeframe |
Baseline, every treatment visit before study drug administration, 30 days after last dose, and every 3 months (up to a maximum of 36 months)
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| Notes [5] - ITT Population |
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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 |
Baseline to the end of the study (up to 49 months)
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Adverse event reporting additional description |
Safety population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Bevacizumab + Paclitaxel + Carboplatin
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Reporting group description |
Participants received bevacizumab 7.5 mg/kg IV on Day 1 of each 3-week cycle for a maximum of 17 cycles. Participants also received paclitaxel (80 mg/m^2 IV) on Days 1, 8, and 15 and carboplatin IV (area under the curve of 6) on Day 1 of each 3-week cycle for a maximum of 8 cycles. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Jul 2009 |
The first amendment (Protocol Version 2) had the following key elements:
- Clarified the definition for date of debulking surgery and staging in participants who had undergone two abdominal operations
- Clarified the presence of symptomatic central nervous system metastases as an exclusion criterion
- Added that a serious active infection requiring intravenous antibiotics at enrollment as an exclusion criterion |
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24 Nov 2009 |
The second amendment (Protocol Version 3) included the following key elements:
- Clarified the treatment duration: Total maximum bevacizumab duration limited to 17 cycles
- Clarified the timing and method of baseline tumor evaluation and collection and grading of adverse events and laboratory parameters
- Clarified that after progression, the only concomitant therapies to be recorded were anti-cancer therapies
- Added guidelines for monitoring serum creatinine, definition of the ITT population, and transfer of the database after final database lock |
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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 | |||
