Trial Outcomes & Findings for Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma (NCT NCT00284141)
NCT ID: NCT00284141
Last Updated: 2012-12-10
Results Overview
OR was either complete response (CR) or partial response (PR) based on RECIST or modified RECIST. CR was the disappearance of all target/nor-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD (According to modified RECIST, to calculate LD for cavitated lesions, the longest cavitation diameters were subtracted from the LD of cavitated target lesions). Assessments were made by the IRC, and confirmed by repeat tumor imaging 4-6 weeks after documentation of the initial response.
COMPLETED
PHASE2
98 participants
up to 2.5 years from initial treatment
2012-12-10
Participant Flow
98 participants were registered into the study, of whom, 96 were exposed to study treatment.
Participant milestones
| Measure |
Aflibercept 4.0 mg/kg
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks until a study withdrawal criterion was met.
|
|---|---|
|
Overall Study
STARTED
|
98
|
|
Overall Study
TREATED
|
96
|
|
Overall Study
ONGOING TREATMENT
|
2
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
98
|
Reasons for withdrawal
| Measure |
Aflibercept 4.0 mg/kg
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks until a study withdrawal criterion was met.
|
|---|---|
|
Overall Study
Disease Progression / Lack of efficacy
|
51
|
|
Overall Study
Adverse Event
|
19
|
|
Overall Study
Participant's request
|
9
|
|
Overall Study
Symptomatic / Clinical Progression
|
11
|
|
Overall Study
Clinical deterioration / death
|
2
|
|
Overall Study
General decline
|
1
|
|
Overall Study
Pneumonia
|
1
|
|
Overall Study
Did not take study medication
|
2
|
|
Overall Study
Ongoing treatment
|
2
|
Baseline Characteristics
Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma
Baseline characteristics by cohort
| Measure |
Aflibercept 4.0 mg/kg
n=98 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks until a study withdrawal criterion was met.
|
|---|---|
|
Age Continuous
|
60.2 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
79 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian, Oriental
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: Simon's cohort: The first 84 evaluable participants, based on Simon's two-stage study design that required 84 evaluable participants to maintain a targeted 90% power.
OR was either complete response (CR) or partial response (PR) based on RECIST or modified RECIST. CR was the disappearance of all target/nor-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD (According to modified RECIST, to calculate LD for cavitated lesions, the longest cavitation diameters were subtracted from the LD of cavitated target lesions). Assessments were made by the IRC, and confirmed by repeat tumor imaging 4-6 weeks after documentation of the initial response.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=84 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
n=84 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Confirmed Objective Response (OR) Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Independent Review Committee (IRC).
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: Simon's cohort: The first 84 evaluable participants, based on Simon's two-stage study design that required 84 evaluable participants to maintain a targeted 90% power.
OR was either complete response (CR) or partial response (PR) based on RECIST or modified RECIST. CR was the disappearance of all target/nor-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD (According to modified RECIST, to calculate LD for cavitated lesions, the longest cavitation diameters were subtracted from the LD of cavitated target lesions). Assessments were made by the Investigator, and confirmed by repeat tumor imaging 4-6 weeks after documentation of the initial response.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=84 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
n=84 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Confirmed Objective Response Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Investigator.
Objective response (OR)
|
2 participants
|
2 participants
|
|
Confirmed Objective Response Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Investigator.
Complete response (CR)
|
0 participants
|
0 participants
|
|
Confirmed Objective Response Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Investigator.
Partial response (PR)
|
2 participants
|
2 participants
|
SECONDARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: No modified RECIST responses, as confirmed by the IRC review, were observed. Only 2 responders were reported by the Investigators. Therefore, the analyses for duration of response was not performed.
DR was the time interval from the first complete response (CR) or partial response (PR) to the date of tumor progression or death from any cause, whichever was earlier. The duration of response was calculated only for those participants who achieved CR or PR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: All registered participants. 18 participants were censored.
PFS time was interval from the date of registration to the date of tumor progression (by RECIST or modified RECIST), or death from any cause, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots. Progression was at least a 20% increase in the sum of the longest diameter (LD) of tumors, compared to smallest sum LD recorded since treatment started, or the appearance of one or more new tumors. If a participant did not progress or die, the date was censored to the date of last valid tumor assessment or the date of data cut-off, whichever was earlier.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=80 Participants with PFS Events
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
n=80 Participants with PFS Events
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Progression-free Survival (PFS) Time Assessed by the Independent Review Committee (IRC)
|
11.3 weeks
Interval 9.3 to 16.1
|
11.3 weeks
Interval 9.3 to 16.1
|
SECONDARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: All registered participants. 17 participants were censored.
PFS time was interval from the date of registration to the date of tumor progression (by RECIST or modified RECIST), or death from any cause, whichever was earlier. If a participant did not progress or die, the date was censored to the date of last valid tumor assessment or the date of data cut-off, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots. Progression was at least a 20% increase in the sum of the longest diameter (LD) of tumors, compared to smallest sum LD recorded since treatment started, or the appearance of one or more new tumors.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=81 Participants with PFS Events
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
n=81 Participants with PFS Events
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Progression-free Survival (PFS) Time Assessed by the Investigator
|
12.0 weeks
Interval 10.0 to 16.0
|
11.9 weeks
Interval 9.7 to 14.7
|
SECONDARY outcome
Timeframe: up to 2.5 years from initial treatmentPopulation: All registered participants. 38 participants were censored for OS.
OS was the time interval between registration to the date of death from any cause. The median time for OS was estimated from Kaplan-Meier Plots. A participant was to be censored for the OS analysis if the participant was alive by the study cut-off date. The censoring date was either the date that the participant was last known to be alive or the date of study cut-off, whichever came earlier.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=60 Participant with OS Event (death)
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Overall Survival (OS)
|
26.9 months
Interval 21.0 to 49.3
|
—
|
SECONDARY outcome
Timeframe: Baseline to 2.5 yearsPopulation: All registered participants with available questionnaires at the timepoint assessed.
HRQL was assessed with the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) questionnaire, which was completed by the participants on Day 1 of Cycle 1 only (for baseline value), then on Day 14 of each even-numbered cycle to evaluate the participants symptoms. The questionnaire scored 7 symptoms: shortness of breath, weight loss, clarity in thinking, coughing, appetite, chest tightness, ease of breathing, on a 0-4 scale. The total FACT-LCS score ranged from 0-28 (where 28 was related to the worst outcome). To calculate a change, the baseline score was subtracted from the score obtained after treatment. A negative value implied an improvement in HRQL.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=83 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline at Cycle 4 (N=41)
|
-1.9 score on a scale
Standard Deviation 4.7
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline at Cycle 6 (N=25)
|
-1.0 score on a scale
Standard Deviation 5.0
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline at Cycle 8 (N=13)
|
-1.4 score on a scale
Standard Deviation 4.7
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline at Cycle 10 (N=10)
|
-1.7 score on a scale
Standard Deviation 6.9
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline to last assessment (N=70)
|
-3.3 score on a scale
Standard Deviation 5.2
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Baseline FACT-LCS Score (N=83)
|
19.9 score on a scale
Standard Deviation 3.9
|
—
|
|
Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale
Change from baseline at Cycle 2 (N=58)
|
-1.5 score on a scale
Standard Deviation 3.6
|
—
|
SECONDARY outcome
Timeframe: up to 60+/-5 days after treatment discontinuation, or or until TEAE was resolved or stabilized (Collected till 18 July 2008)Population: All participants who received at least part of 1 dose of study treatment.
All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 60 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=96 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Overall Safety - Number of Participants With Adverse Events
With any TEAE
|
96 participants
|
—
|
|
Overall Safety - Number of Participants With Adverse Events
With any Serious TEAE
|
47 participants
|
—
|
|
Overall Safety - Number of Participants With Adverse Events
With any TEAE leading to Death
|
16 participants
|
—
|
|
Overall Safety - Number of Participants With Adverse Events
with any TEAE leading to Treatment discontinuation
|
19 participants
|
—
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: All participants who received at least part of 1 dose of study treatment.
Participants with abnormal laboratory results for * Liver and renal function (Alkaline phosphatase, Alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], Creatinine, Hyperbilirubinemia), * Electrolytes (Hypercalcemia, Hypocalcemia, Hypokalemia, Hypernatremia, Hyponatremia, Hypophosphatemia) * Metabolism (Hypoalbuminemia, Hyperglycemia, Hypoglycemia) * Hematology (Partial thromboplastin time, Anemia, Lymphopenia, Neutropenia, Thrombocytopenia, Leukopenia)
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=96 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hypercalcemia
|
6 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hypocalcemia
|
15 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hypokalemia
|
10 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hyponatremia
|
41 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hypophosphatemia (N=91)
|
14 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Lymphopenia (N=84)
|
60 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Leukopenia
|
11 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
LIVER AND RENAL FUNCTION- Alkaline Phosphatase
|
39 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
LIVER AND RENAL FUNCTION - ALT
|
35 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
LIVER AND RENAL FUNCTION - AST
|
37 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
LIVER AND RENAL FUNCTION - Creatinine
|
15 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
LIVER AND RENAL FUNCTION - Hyperbilirubinemia
|
4 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hyperkalemia
|
24 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
ELECTROLYTES - Hypernatremia
|
5 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
METABOLISM - Hypoalbuminemia (N=91)
|
44 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
METABOLISM - Hyperglycemia
|
81 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
METABOLISM - Hypoglycemia
|
10 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Partial thromboplastin time (N=81)
|
30 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Anemia
|
34 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Neutropenia (N=78)
|
4 Participants
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY - Thrombocytopenia
|
11 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 of the first infusion of Aflibercept (cycle 1)Population: All participants who received at least part of 1 dose of study treatment and had evaluable blood samples.
Plasma free aflibercept levels after the first aflibercept infusion were estimated by a validated direct measured by enzyme-linked immunosorbent assay (ELISA), with a limit of quantification (LOQ) of 15.6 ng/mL.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=47 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Peak of Free Aflibercept (VEGF Trap)
|
71.4 micrograms/mL
Standard Deviation 31.8
|
—
|
SECONDARY outcome
Timeframe: At the end of each treatment cycle (up to 2.5 years)Population: All participants who received at least part of 1 dose of study treatment and had evaluable blood samples on Day 1 of Cycle 3 for measurement of VEGF-bound aflibercept.
Median free and VEGF-bound trough concentrations were determined at the end of each cycle beyond Cycle 2 (Steady-state) for each participant. Plasma free aflibercept levels were estimated by a validated direct ELISA, with an LOQ of 15.6 ng/mL. Plasma VEGF-bound aflibercept levels were also estimated by a separate validated direct ELISA with an LOQ of 43.9 ng/mL. Mean ± SD (coefficient of variation \[CV%\]) values were estimated from the median values calculated for each participant.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=61 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Free and VEGF-bound Trough Aflibercept Concentrations (VEGF Trap)
Trough free aflibercept concentration
|
9.53 micrograms/mL
Standard Deviation 6.28
|
—
|
|
Free and VEGF-bound Trough Aflibercept Concentrations (VEGF Trap)
Trough VEGF-bound aflibercept concentration
|
3.48 micrograms/mL
Standard Deviation 1.04
|
—
|
SECONDARY outcome
Timeframe: up to 2.5 years after initial treatmentPopulation: All participants who received at least part of 1 dose of study treatment and had evaluable blood samples.
Anti-drug antibodies in a participant's serum sample were assayed with an anti-drug ELISA assay, with a lower limit of quantitation of 238.4 ng/mL for an undiluted human serum sample. Serum for anti-drug antibody analysis was collected pre-dose on every fourth cycle after Cycle 1 Day 1 (at 8 week intervals), at end of treatment (EOT), and during post-treatment follow-up 60 days after the last dose.
Outcome measures
| Measure |
Aflibercept 4.0 mg/kg Arm Assessed by Modified RECIST
n=80 Participants
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by RECIST criteria.
|
Aflibercept 4.0 mg/kg Arm Assessed by RECIST
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks assessed by modified RECIST criteria.
|
|---|---|---|
|
Number of Participants With Anti-drug Antibodies
|
0 participants
|
—
|
Adverse Events
4 mg/kg
Serious adverse events
| Measure |
4 mg/kg
n=96 participants at risk
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks until a study withdrawal criterion was met.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Cardiac disorders
Atrial flutter
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Cardiac disorders
Cardiac failure congestive
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Cardiac disorders
Cardiomyopathy
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Dysphagia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Nausea
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Obstruction gastric
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Asthenia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Disease progression
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Fatigue
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Non-cardiac chest pain
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Cellulitis
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Pneumonia
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Sepsis
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Injury, poisoning and procedural complications
Fall
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Injury, poisoning and procedural complications
Radiation injury
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Investigations
Blood creatinine increased
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Nervous system disorders
Cerebral ischaemia
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Nervous system disorders
Cerebrovascular accident
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Psychiatric disorders
Anxiety
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Psychiatric disorders
Mental status changes
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Renal and urinary disorders
Bladder stenosis
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Renal and urinary disorders
Hydronephrosis
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Renal and urinary disorders
Urinary retention
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.2%
4/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Vascular disorders
Axillary vein thrombosis
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
|
Vascular disorders
Deep vein thrombosis
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Vascular disorders
Hypertension
|
2.1%
2/96 • From treatment initiation to February 24, 2009.
|
|
Vascular disorders
Superior vena caval occlusion
|
1.0%
1/96 • From treatment initiation to February 24, 2009.
|
Other adverse events
| Measure |
4 mg/kg
n=96 participants at risk
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every 2 weeks until a study withdrawal criterion was met.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Constipation
|
28.1%
27/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
12/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Dry mouth
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Dysphagia
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Nausea
|
24.0%
23/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Oral pain
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
16/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Asthenia
|
16.7%
16/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Chest pain
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Disease progression
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Fatigue
|
40.6%
39/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Mucosal inflammation
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Oedema peripheral
|
20.8%
20/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Pain
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
General disorders
Pyrexia
|
11.5%
11/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Pneumonia
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Infections and infestations
Urinary tract infection
|
11.5%
11/96 • From treatment initiation to February 24, 2009.
|
|
Investigations
Weight decreased
|
9.4%
9/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
24/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.4%
9/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Dehydration
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.6%
14/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.4%
10/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
Nervous system disorders
Dizziness
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Nervous system disorders
Headache
|
39.6%
38/96 • From treatment initiation to February 24, 2009.
|
|
Psychiatric disorders
Anxiety
|
7.3%
7/96 • From treatment initiation to February 24, 2009.
|
|
Psychiatric disorders
Depression
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Psychiatric disorders
Insomnia
|
10.4%
10/96 • From treatment initiation to February 24, 2009.
|
|
Renal and urinary disorders
Proteinuria
|
15.6%
15/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.9%
22/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
28.1%
27/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
38.5%
37/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.8%
19/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
11.5%
11/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.2%
5/96 • From treatment initiation to February 24, 2009.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.2%
6/96 • From treatment initiation to February 24, 2009.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
8/96 • From treatment initiation to February 24, 2009.
|
|
Vascular disorders
Hypertension
|
39.6%
38/96 • From treatment initiation to February 24, 2009.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days for abstracts) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
- Publication restrictions are in place
Restriction type: OTHER