Trial Outcomes & Findings for Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer (NCT NCT02776683)
NCT ID: NCT02776683
Last Updated: 2019-11-21
Results Overview
The primary safety endpoint of the trial was patients with any of the following selected adverse events (AEs): * Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions), * Thromboembolic events (arterial or venous), * Gastrointestinal perforations, * Hypertension, * Proteinuria, * Pulmonary hemorrhage * All hemorrhages (including pulmonary hemorrhages) * Wound-healing complications/abscess/fistulas * Posterior reversible encephalopathy syndrome * Ovarian failure. All AEs with an onset between start of treatment and end of the residual effect period (REP), a period of 18 weeks after the last dose of trial medication were considered for the primary safety analysis. Confidence interval was calculated using Wilson score method.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
123 participants
Primary outcome timeframe
From baseline up to 18 weeks after the last dose of trial medication prior to the Switch Visit. Maximum duration of up to 32 treatment cycles + safety follow up (up to 82 weeks overall).
Results posted on
2019-11-21
Participant Flow
This was Phase IIIb, open-label, multicenter, multinational, single-arm trial. Patients with previously untreated metastatic colorectal cancer (mCRC) were enrolled. From 21December2017, Sponsor recommended that patients should be switched from BI 695502 to the reference product Avastin® as soon as it was available at the respective clinical site.
All patients were screened for eligibility to participate in the trial. Patients attended specialist sites which would then ensure that they (the patient) met all strictly implemented inclusion/exclusion criteria. Patients were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Participant milestones
| Measure |
BI 695502
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
BI 695502 to Avastin®
At the switch visit, patients were to be switched from BI 695502 to Avastin®. Post-switch, patients were to receive Avastin® (5 mg/kg) solution for i.v. infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier.
|
|---|---|---|
|
Pre-switch Period
STARTED
|
123
|
0
|
|
Pre-switch Period
COMPLETED
|
43
|
0
|
|
Pre-switch Period
NOT COMPLETED
|
80
|
0
|
|
Post-switch Period
STARTED
|
0
|
43
|
|
Post-switch Period
COMPLETED
|
0
|
0
|
|
Post-switch Period
NOT COMPLETED
|
0
|
43
|
Reasons for withdrawal
| Measure |
BI 695502
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
BI 695502 to Avastin®
At the switch visit, patients were to be switched from BI 695502 to Avastin®. Post-switch, patients were to receive Avastin® (5 mg/kg) solution for i.v. infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier.
|
|---|---|---|
|
Pre-switch Period
Protocol Violation
|
1
|
0
|
|
Pre-switch Period
Adverse Event
|
21
|
0
|
|
Pre-switch Period
Withdrawal by Subject
|
9
|
0
|
|
Pre-switch Period
Physician Decision
|
7
|
0
|
|
Pre-switch Period
Progressive disease
|
39
|
0
|
|
Pre-switch Period
Other than listed
|
3
|
0
|
|
Post-switch Period
Adverse Event
|
0
|
3
|
|
Post-switch Period
Withdrawal by Subject
|
0
|
2
|
|
Post-switch Period
Physician Decision
|
0
|
3
|
|
Post-switch Period
Progressive disease
|
0
|
20
|
|
Post-switch Period
Other than listed
|
0
|
15
|
Baseline Characteristics
Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Age, Continuous
|
58.0 Years
STANDARD_DEVIATION 11.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
106 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
82 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline up to 18 weeks after the last dose of trial medication prior to the Switch Visit. Maximum duration of up to 32 treatment cycles + safety follow up (up to 82 weeks overall).Population: Treated set (TS): The TS contained all patients who signed informed consent and who received at least one dose of trial medication.
The primary safety endpoint of the trial was patients with any of the following selected adverse events (AEs): * Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions), * Thromboembolic events (arterial or venous), * Gastrointestinal perforations, * Hypertension, * Proteinuria, * Pulmonary hemorrhage * All hemorrhages (including pulmonary hemorrhages) * Wound-healing complications/abscess/fistulas * Posterior reversible encephalopathy syndrome * Ovarian failure. All AEs with an onset between start of treatment and end of the residual effect period (REP), a period of 18 weeks after the last dose of trial medication were considered for the primary safety analysis. Confidence interval was calculated using Wilson score method.
Outcome measures
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Patients with any of the selected AEs
|
58.5 Percentage of participants (%)
Interval 49.7 to 66.86
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Proteinuria
|
9.8 Percentage of participants (%)
Interval 5.67 to 16.28
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Hemorrhages
|
22.80 Percentage of participants (%)
Interval 16.25 to 30.93
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Wound-healing complications
|
1.6 Percentage of participants (%)
Interval 0.45 to 5.74
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Ovarian failure
|
0.00 Percentage of participants (%)
Interval 0.0 to 6.53
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Infusion reactions
|
18.7 Percentage of participants (%)
Interval 12.8 to 26.5
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Thromboembolic events
|
12.2 Percentage of participants (%)
Interval 7.53 to 19.15
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Gastrointestinal perforations
|
2.4 Percentage of participants (%)
Interval 0.83 to 6.93
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Hypertension
|
28.5 Percentage of participants (%)
Interval 21.23 to 36.99
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Pulmonary Haemorrhage
|
0.00 Percentage of participants (%)
Interval 0.0 to 3.03
|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Reversible Encephalopathy Syndrome
|
0.0 Percentage of participants (%)
Interval 0.0 to 3.03
|
SECONDARY outcome
Timeframe: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).Population: TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication. Only patients with complete or partial objective response were included in the analysis.
DOR was the time from first documented Complete Response (CR) (CR is disappearance of all target lesions) or Partial Response (PR) (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) until time of progression as assessed by central imaging review per Response evaluation criteria in solid tumors (RECIST) 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. DOR was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.
Outcome measures
| Measure |
BI 695502
n=77 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Duration of Response (DOR) as Assessed by Central Imaging Review
|
9.1 Months
Interval 7.3 to
The upper limit confidence interval was not determined as it was not reached
|
SECONDARY outcome
Timeframe: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).Population: TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication.
TTP was defined as the time from first administration of trial medication to the date of tumor progression as assessed by central imaging review per RECIST 1.1 (RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.). TTP was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.
Outcome measures
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Time to Progression (TTP) as Assessed by Central Imaging Review
|
11.1 Months
Interval 9.5 to 12.9
|
SECONDARY outcome
Timeframe: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).Population: TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication.
OR rate was defined as the percentage of patients who achieved at least one visit response of CR (CR is disappearance of all target lesions) or PR (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) after the start of treatment. The response criteria evaluation was carried out according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Confidence interval was calculated using Wilson score method. The definition for OR (CR/PR) extends until disease progression/ death/ unacceptable toxicity/ end of the trial, whichever occurred earlier. However for "Duration of response" this censoring does not apply. Hence the apparent discrepancy. OR = CR + PR.
Outcome measures
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Objective Response (OR) Rate as Assessed by Central Imaging Review
|
61.0 Percentage of participants
Interval 52.1 to 69.1
|
SECONDARY outcome
Timeframe: From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).Population: TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication.
OS was defined as the time from first administration of trial medication until death from any cause. OS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.
Outcome measures
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Overall Survival (OS) Time
|
19.4 Months
Interval 16.7 to 21.1
|
SECONDARY outcome
Timeframe: Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).Population: TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication.
PFS was defined as the time from first administration of trial medication until disease progression as assessed by central imaging review or death due to any cause. Disease progression was assessed according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. PFS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.
Outcome measures
| Measure |
BI 695502
n=123 Participants
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Progression-Free Survival (PFS) Time as Assessed by Central Imaging Review
|
10.5 Months
Interval 9.4 to 11.8
|
Adverse Events
BI 695502
Serious events: 33 serious events
Other events: 118 other events
Deaths: 41 deaths
Serious adverse events
| Measure |
BI 695502
n=123 participants at risk
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Infections and infestations
Sepsis
|
1.6%
2/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Infections and infestations
Bacterial sepsis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Infections and infestations
Biliary tract infection
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Infections and infestations
Device related infection
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Infections and infestations
Gastroenteritis viral
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Infections and infestations
Vulval abscess
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma benign
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.6%
2/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Hypersplenism
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Immune system disorders
Drug hypersensitivity
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Immune system disorders
Hypersensitivity
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Cervical radiculopathy
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Myelopathy
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Seizure
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Spinal cord compression
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Deep vein thrombosis
|
1.6%
2/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Accelerated hypertension
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Brachiocephalic vein thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Pelvic venous thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Vena cava thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.9%
6/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Ileus
|
1.6%
2/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Intra-abdominal fluid collection
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Large intestinal stenosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Vomiting
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
0.00%
0/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Hepatobiliary disorders
Liver disorder
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Renal and urinary disorders
Renal haematoma
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.81%
1/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
Other adverse events
| Measure |
BI 695502
n=123 participants at risk
All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.
|
|---|---|
|
Infections and infestations
Urinary tract infection
|
6.5%
8/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Neutropenia
|
26.0%
32/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Anaemia
|
17.1%
21/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.3%
20/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.1%
26/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.1%
10/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Psychiatric disorders
Insomnia
|
7.3%
9/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
35.8%
44/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Neuropathy peripheral
|
17.1%
21/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Dysgeusia
|
14.6%
18/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Headache
|
11.4%
14/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Dizziness
|
6.5%
8/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Nervous system disorders
Neurotoxicity
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Vascular disorders
Hypertension
|
27.6%
34/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.6%
18/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.5%
8/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Nausea
|
46.3%
57/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
41/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Stomatitis
|
30.1%
37/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Constipation
|
22.0%
27/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Vomiting
|
15.4%
19/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Abdominal pain
|
13.8%
17/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.8%
12/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.3%
9/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.0%
16/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
8.9%
11/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.3%
9/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.3%
9/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Renal and urinary disorders
Proteinuria
|
8.9%
11/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
General disorders
Fatigue
|
36.6%
45/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
General disorders
Pyrexia
|
13.8%
17/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
General disorders
Malaise
|
8.1%
10/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
General disorders
Asthenia
|
7.3%
9/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Neutrophil count decreased
|
20.3%
25/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Platelet count decreased
|
14.6%
18/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Weight decreased
|
14.6%
18/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
White blood cell count decreased
|
14.6%
18/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.8%
12/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Aspartate aminotransferase increased
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
|
Investigations
Weight increased
|
5.7%
7/123 • From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER