Trial Outcomes & Findings for A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer (NCT NCT01239732)
NCT ID: NCT01239732
Last Updated: 2016-06-10
Results Overview
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1021 participants
Primary outcome timeframe
Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
Results posted on
2016-06-10
Participant Flow
This study has been completed. However, the efficacy and safety results up to the clinical database cutoff date of 07 December 2014 are provided.
Participant milestones
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
Participants received bevacizumab 15 milligrams/kilogram (mg/kg) intravenously (IV) on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 milligram per square meter (mg/m\^2) IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (area under the plasma concentration-time curve \[AUC\] 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Overall Study
STARTED
|
1021
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
1021
|
Reasons for withdrawal
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
Participants received bevacizumab 15 milligrams/kilogram (mg/kg) intravenously (IV) on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 milligram per square meter (mg/m\^2) IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (area under the plasma concentration-time curve \[AUC\] 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Overall Study
Termination of study per protocol
|
667
|
|
Overall Study
Death
|
226
|
|
Overall Study
Withdrawal by Subject
|
87
|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Protocol Violation
|
3
|
|
Overall Study
Participant non compliance
|
5
|
|
Overall Study
Study termination by sponsor
|
2
|
|
Overall Study
Investigator's decision
|
4
|
|
Overall Study
Treatment failure
|
2
|
|
Overall Study
Other
|
19
|
Baseline Characteristics
A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Age, Continuous
|
56.3 years
STANDARD_DEVIATION 10.98 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1021 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)Population: Safety population
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Percentage of Participants With at Least One Adverse Event (AE)
|
97.8 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 yearsPopulation: Intent to treat population included all participants who received at least one dose of study medication.
PFS was defined as the time between the date of first administration of any study treatment and the date of first documented protocol-defined disease progression (that is \[i.e.\], radiologically by Response Evaluation Criteria In Solid Tumors \[RECIST\], clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. Kaplan-Meier estimation was used for median time to PFS.
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Progression-Free Survival (PFS)
|
25.5 months
Interval 23.7 to 27.6
|
SECONDARY outcome
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks (Q26W) after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 yearsPopulation: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
Best overall response (BOR) according to RECIST Version 1.0 was categorized as: CR, PR, progressive disease (PD), stable disease (SD). CR: disappearance of all target lesions and non-target lesions. PR: \>=30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions. PD: Natural progression or deterioration of the malignancy under study (including new sites of metastasis). SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Participants with a BOR of CR and PR were defined as responders, while participants with a BOR of SD, PD, or unable to assess were defined as non-responders.
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=421 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0
|
72.7 percentage of participants
Interval 68.2 to 76.9
|
SECONDARY outcome
Timeframe: 3 days prior to Day 1 of every cycle, then every 6 weeks (Q6W) during the first year, every 3 months (Q3M) in the second and third year, every 6 months (Q6M) in the fourth year of the study (until data cutoff 07 December 2014, up to 4 years)Population: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days. Overall response according to CA-125 was only evaluated for participants with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the upper limit of normal (ULN).
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=340 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Percentage of Participants Achieving an Overall Response by 50% Carcinoma Antigen 125 (CA-125) Response Criteria
|
91.8 percentage of participants
Interval 88.3 to 94.5
|
SECONDARY outcome
Timeframe: RECIST: Day 1, at end of Cycles 3 and 6, then every 6 cycles, at bevacizumab cessation, Q26W after cessation; CA-125: 3 days before Day 1 of every cycle, then Q6W(1st year), Q3M(2nd-3rd year), Q6M(4th year); until data cutoff 07Dec2014, up to 4 yearsPopulation: ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome.
Overall response was only evaluated for participants who were evaluable according to RECIST v1.0 with a measurable disease at baseline and/or according to CA-125 with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the ULN. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (\>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions). CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days.
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=578 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Percentage of Participants Achieving an Overall Response by RECIST Version 1.0 and/or 50% CA-125 Response Criteria
|
82.4 percentage of participants
Interval 79.0 to 85.4
|
SECONDARY outcome
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 yearsPopulation: ITT population
DOR was defined as the time from the first documented response (CR or PR per RECIST v1.0), to the first documented protocol-defined disease progression (i.e., radiologically by RECIST, clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (\>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions). Disease progression: Natural progression or deterioration of the malignancy under study (including new sites of metastasis).
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Duration of Objective Response (DOR)
|
18.2 months
Interval 16.6 to 19.6
|
SECONDARY outcome
Timeframe: First administration of any study treatment until death or data cutoff 07 December 2014, up to 4 yearsPopulation: ITT population
OS was defined as the time from the date of the first administration of any study treatment to the date of death, regardless of the cause of death. Participants without the event of death were censored at the last date in the study, defined as the latest date of the following: the date of first administration of study treatment, date of last study treatment, date of last visit, or date last known to be alive. Kaplan-Meier estimation was used for OS.
Outcome measures
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 Participants
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Overall Survival (OS)
|
NA months
The median and 95% confidence interval were not calculable because less than 50% of participants had the event.
|
SECONDARY outcome
Timeframe: 3 days prior to Day 1 of every cycle, then every 6 weeks during the first year, every 3 months in the second and third year, every 6 months in the fourth year of the study (until data cutoff 07 December 2014, up to 4 years)Population: Previous studies linking CA-125 levels with bevacizumab exposure as a potential secondary outcome measure for PFS did not produce any reliable information. Therefore, it was decided that data for this outcome measure should not be analyzed, as agreed with the study steering committee.
Biological progression-free interval is 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. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for participants with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for participants with elevated CA-125 pre-treatment and initial normalization of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per participant on 2 occasions at least 1 week apart (for participants with elevated CA-125 pre-treatment which never normalized).
Outcome measures
Outcome data not reported
Adverse Events
Bevacizumab + Paclitaxel + Carboplatin
Serious events: 285 serious events
Other events: 980 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 participants at risk
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
13/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.1%
11/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Ileus
|
0.88%
9/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Subileus
|
0.88%
9/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.78%
8/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.78%
8/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Constipation
|
0.59%
6/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Vomiting
|
0.49%
5/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Nausea
|
0.39%
4/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Ascites
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal incarcerated hernia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Anal fistula
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Dysphagia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Enterocolitis haemorrhagic
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Faecaloma
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastric stenosis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Haemorrhoids thrombosed
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Jejunal perforation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Mallory-weiss syndrome
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Oesophagitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Pancreatitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.4%
25/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.1%
21/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Anaemia
|
1.6%
16/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.3%
13/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Pneumonia
|
0.49%
5/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Urinary tract infection
|
0.49%
5/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Infected lymphocele
|
0.39%
4/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Proctitis infectious
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Infection
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Cellulitis
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Gastroenteritis
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Nasopharyngitis
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Abdominal wall abscess
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Anal abscess
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Device related infection
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Influenza
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Lung infection
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Pelvic abscess
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Pharyngitis
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Sepsis
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Abdominal infection
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Abdominal sepsis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Acute hepatitis C
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Arthritis infective
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Bronchitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Catheter site infection
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Cholecystitis inefective
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Clostridium difficile infection
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Colonic abscess
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Cystitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Enterocolitis infectious
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Gastroenteritis viral
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Gingivitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Groin abscess
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Infected cyst
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Parotid abscess
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Peritoneal abscess
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Peritonitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Postoperative wound infection
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Septic shock
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Staphylococcal infection
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Subdiaphragmatic abscess
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Urosepsis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Vulval cellulitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Hypertension
|
1.6%
16/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Embolism venous
|
0.88%
9/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Lymphocele
|
0.78%
8/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Deep vein thrombosis
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Embolism arterial
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Lymphoedema
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Arterial thrombosis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Hypovolaemic shock
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Malignant hypertension
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Orthostatic hypotension
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Thrombophlebitis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Venous thrombosis limb
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Pyrexia
|
0.59%
6/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
General physical health deterioration
|
0.39%
4/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Asthenia
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Chest pain
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Impaired healing
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Death
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Fatigue
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Mucosal inflammation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Oedema peripheral
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Performance status decreased
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Headache
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Transient ischaemic attack
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Presyncope
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Tubulointerstitial nephritis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Cerebral ischaemia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Cerebrovascular disorder
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Lacunar infarction
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Leukoencephalopathy
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Sciatica
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Syncope
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.78%
8/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Seroma
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Acute myocardial infarction
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Cardiac failure congestive
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Myocardial infarction
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Angina pectoris
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Atrial fibrillation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Coronary artery disease
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Cardiac disorders
Tachycardia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Proteinuria
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Renal failure
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Calculus ureteric
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Glomerulonephritis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Hydronephrosis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Renal infarct
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Nicotinic acid deficiency
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.29%
3/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Paraneoplastic dermatomyositis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Rheumatic disorder
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Alanine aminotransferase abnormal
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Alanine aminotransferase increased
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Aspartate aminotransferase abnormal
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Aspartate aminotransferase increased
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Blood alkaline phosphatase abnormal
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
General physical condition abnormal
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Weight decreased
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Psychiatric disorders
Suicide attempt
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Psychiatric disorders
Bruxism
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Psychiatric disorders
Major depression
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer recurrent
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer recurrent
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Reproductive system and breast disorders
Female genital tract fistula
|
0.20%
2/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Immune system disorders
Drug hypersensitivity
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Surgical and medical procedures
Intestinal operation
|
0.10%
1/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
Other adverse events
| Measure |
Bevacizumab + Paclitaxel + Carboplatin
n=1021 participants at risk
Participants received bevacizumab 15 mg/kg IV on Day 1 every 3 weeks from Cycle 1 (1 cycle = 3 weeks) to Cycle 36 (initially concurrent with chemotherapy, then continued as a single agent following the completion of chemotherapy), or until protocol-defined disease progression or until unacceptable toxicity (whichever occurred first). The 15 mg/kg dose every 3 weeks was the recommended dose; however a dose of IV bevacizumab 7.5 mg/kg every 3 weeks was permissible, but was to be selected prior to the first dosing of bevacizumab. Participants received paclitaxel 175 mg/m\^2 IV on Day 1 every 3 weeks or 80 mg/m\^2 IV every week and carboplatin (AUC 5-6) IV on Day 1 every 3 weeks for a minimum of 4 and maximum of 8 cycles (including up to 4 pre-surgical cycles), or until protocol-defined disease progression, or unacceptable toxicity (whichever occurred first).
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
47.5%
485/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Anaemia
|
32.6%
333/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
27.3%
279/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Blood and lymphatic system disorders
Leukopenia
|
10.7%
109/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Nausea
|
38.5%
393/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
25.3%
258/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Constipation
|
25.0%
255/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Vomiting
|
22.5%
230/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal pain
|
21.6%
221/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Stomatitis
|
10.8%
110/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.2%
104/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Gastrointestinal disorders
Gingival bleeding
|
7.3%
75/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Headache
|
23.6%
241/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Neuropathy peripheral
|
19.7%
201/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
15.8%
161/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Paraesthesia
|
13.1%
134/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Dizziness
|
7.3%
75/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Nervous system disorders
Dysgeusia
|
6.7%
68/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Vascular disorders
Hypertension
|
54.1%
552/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Fatigue
|
36.4%
372/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Asthenia
|
13.2%
135/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Mucosal inflammation
|
10.8%
110/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Pyrexia
|
8.4%
86/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
General disorders
Oedema peripheral
|
6.2%
63/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.6%
261/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
18.1%
185/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.5%
138/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.0%
133/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.9%
132/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.1%
52/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
43.3%
442/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.4%
76/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.0%
71/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
29.5%
301/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.2%
94/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.5%
66/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Renal and urinary disorders
Proteinuria
|
31.0%
317/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Urinary tract infection
|
11.9%
122/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Nasopharyngitis
|
8.1%
83/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
60/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Platelet count decreased
|
9.1%
93/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Investigations
Weight increased
|
7.5%
77/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.2%
94/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
|
Psychiatric disorders
Insomnia
|
6.5%
66/1021 • Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER