AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00853372
Collaborator
(none)
85
2
120.9
Study Details
Study Description
Brief Summary
This phase 2 study is an open-label, multi-center study to determine the safety and tolerability of AMG 386 in combination with sunitinib in the treatment of subjects with metastatic renal cell carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
85 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2 Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of Sunitinib Malate in Combination With AMG 386 as First Line or Second Line Therapy for Subjects With Metastatic Renal Cell Carcinoma
Actual Study Start Date
:
May 28, 2009
Actual Primary Completion Date
:
Aug 8, 2011
Actual Study Completion Date
:
Jun 25, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Trebananib 10 mg/kg + Sunitinib Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off |
Drug: Sunitinib
Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of reneal cell cancer (RCC) and will be administered to all participants.
Other Names:
Drug: Trebananib
Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Other Names:
|
| Experimental: Trebananib 15 mg/kg + Sunitinib Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
Drug: Sunitinib
Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of reneal cell cancer (RCC) and will be administered to all participants.
Other Names:
Drug: Trebananib
Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) [From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.]
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: an AE that: is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an other significant medical hazard. Treatment-emergent AEs (TEAEs) are those that occurred after the first administration of study drug through 30 days after the last study drug administration. Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
- Number of Participants With Dose Delays Due to Adverse Events [Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.]
A trebananib dose was considered delayed if it was administered 11 or more days from the previous trebananib infusion. A sunitinib dose was considered delayed if it was administered 3 or more days from the previous dose, except during holidays.
- Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose [first 12 weeks of study treatment]
Participants who had a sunitinib dose modification within 12 weeks from their first dose due to adverse event, laboratory toxicity, or laboratory toxicity and adverse event.
- Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values [From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.]
Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
Secondary Outcome Measures
- Objective Response Rate (ORR) [48 months after last subject enrolled (LSE)]
ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) per modified Response Evaluation Criteria in Solid Tumor (RECIST) criteria (responder). A confirmed CR requires 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. All participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non responders.
- Kaplan-Meier Estimate: Duration of Response (DOR) [48 months after LSE]
DOR was calculated as the time from the first confirmed objective response to first observed disease progression per modified RECIST v. 1.0 criteria or death due to any cause. DOR was calculated only for participants who had an objective response. Objective response was defined as either a confirmed CR or PR per modified RECIST criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR required 2 consecutive assessments at least 28 days apart of PR or CR. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable radiographical disease assessment date.
- Disease Control Rate (DCR) [48 months after LSE]
DCR was defined as the percentage of participants with confirmed CR or PR or stable disease (SD), as defined by modified RECIST v1.0 criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. CR or PR was confirmed at least 28 days after the criteria for response were first met. A response assessment of PR or CR that was not subsequently confirmed at least 4 weeks later were included as SD.
- Kaplan-Meier Estimate: Progression Free Survival (PFS) [48 months after LSE]
PFS was defined as the time from enrollment date to date of disease progression (ie, radiographic progression) per modified RECIST v 1.0 criteria or death. Radiological imaging to assess disease status was performed until participants developed disease progression. Events of radiographic progression per modified RECIST 1.0 that occurred after initiation of subsequent anticancer therapy were not considered PFS events. Deaths occurring after initiation of subsequent anticancer therapy were considered PFS events. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
- Kaplan-Meier Estimate: Overall Survival (OS) [48 months after LSE]
The time from enrollment date to date of death. Participants who had not died by the analysis data cutoff date were censored at their last contact date.
- Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir [Baseline, 48 months after LSE]
Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions.
- Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time [Pre-infusion and up to 10 minutes post-infusion on Weeks 1, 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)]
- Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time [Pre-infusion on Weeks 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)]
- Pharmacokinetic Parameter: Cmin for Sunitinib Over Time [Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)]
- Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time [Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug)]
- Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline [48 months after LSE]
Transient positive results were defined as a positive post-baseline result followed by a negative result at the participant's last time point tested within the study period.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects must have a histologically confirmed metastatic renal cell cancer (RCC) with a clear cell component
-
Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification
-
Measurable disease with at least one unidimensionally measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) guidelines with modifications
-
Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening
-
Eastern Cooperative Oncology Group (ECOG) of 0 or 1
Exclusion Criteria:
Disease related
-
Known history of central nervous system metastases.
-
Previous treatment (excluding surgery, prior cytokine-based immunotherapy and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
-
Focal radiation therapy for palliation of pain from bony metastases within 14 days of enrollment.
Medications
-
Currently or previously treated with sunitinib or other small molecule inhibitors of vascular endothelial growth factor (VEGF)
-
Currently or previously treated with agents that neutralizing VEGF
-
Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
-
Currently or previously treated with agents inhibiting the mammalian target of rapamycin (mTOR)
-
Current or within 30 days prior to enrollment treatment with immune modulators
-
Concomitant or previous use within 30 days prior to enrollment of any strong inducer of CYP3A4
-
Concomitant or previous use of amiodarone within 6 months prior to enrollment
General medical
-
Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
-
Major surgery within 28 days prior to enrollment or still recovering from prior surgery
-
Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted.
Other
-
Other investigational procedures are excluded
-
Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
Other inclusion/exclusion criteria may apply, per protocol.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00853372
Other Study ID Numbers:
- 20080579
First Posted:
Mar 2, 2009
Last Update Posted:
Jul 1, 2020
Last Verified:
May 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 18 sites in the United States, Australia, Belgium, France, and Poland. The first participant was enrolled on 28 May 2009. The last participant was enrolled on 29 November 2010. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Period Title: Overall Study | ||
| STARTED | 43 | 42 |
| COMPLETED | 11 | 13 |
| NOT COMPLETED | 32 | 29 |
Baseline Characteristics
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib | Total |
|---|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Total of all reporting groups |
| Overall Participants | 43 | 42 | 85 |
| Age, Customized (participants) [Number] | |||
| < 65 years |
30
69.8%
|
27
64.3%
|
57
67.1%
|
| >= 65 years |
13
30.2%
|
15
35.7%
|
28
32.9%
|
| < 75 years |
41
95.3%
|
40
95.2%
|
81
95.3%
|
| >= 75 years |
2
4.7%
|
2
4.8%
|
4
4.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
5
11.6%
|
10
23.8%
|
15
17.6%
|
| Male |
38
88.4%
|
32
76.2%
|
70
82.4%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White or Caucasian |
41
95.3%
|
42
100%
|
83
97.6%
|
| Black or African American |
1
2.3%
|
0
0%
|
1
1.2%
|
| Hispanic or Latino |
1
2.3%
|
0
0%
|
1
1.2%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Japanese |
0
0%
|
0
0%
|
0
0%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Aborigine |
0
0%
|
0
0%
|
0
0%
|
| Other, Not Specified |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs) |
|---|---|
| Description | AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: an AE that: is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an other significant medical hazard. Treatment-emergent AEs (TEAEs) are those that occurred after the first administration of study drug through 30 days after the last study drug administration. Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death). |
| Time Frame | From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| TEAEs, All |
43
100%
|
42
100%
|
| TEAEs, Grade ≥ 3 |
32
74.4%
|
34
81%
|
| TEAEs, Grade ≥ 4 |
4
9.3%
|
7
16.7%
|
| TEAEs, Fatal AEs |
1
2.3%
|
1
2.4%
|
| TEAEs, SAEs |
17
39.5%
|
26
61.9%
|
| TEAEs Leading to (→) DC of Trebananib |
7
16.3%
|
14
33.3%
|
| TEAEs → DC of Trebananib, Serious |
5
11.6%
|
12
28.6%
|
| TEAEs → DC of Trebananib, Non-Serious |
2
4.7%
|
2
4.8%
|
| TEAEs → DC of Sunitinib |
9
20.9%
|
16
38.1%
|
| TEAEs → DC of Sunitinib, Serious |
5
11.6%
|
12
28.6%
|
| TEAEs → DC of Sunitinib, Non-Serious |
4
9.3%
|
5
11.9%
|
| TEAEs → DC of All Treatment |
6
14%
|
14
33.3%
|
| TEAEs → DC of All Treatment, Serious |
5
11.6%
|
12
28.6%
|
| TEAEs → DC of All Treatment, Non-Serious |
1
2.3%
|
2
4.8%
|
| Treatment-Related (TR) TEAEs, All |
43
100%
|
42
100%
|
| TR TEAEs, Grade ≥ 3 |
25
58.1%
|
31
73.8%
|
| TR TEAEs, Grade ≥ 4 |
2
4.7%
|
5
11.9%
|
| TR TEAEs, Fatal AEs |
0
0%
|
1
2.4%
|
| TR TEAEs, SAEs |
11
25.6%
|
18
42.9%
|
| TR TEAEs → DC of Trebananib |
6
14%
|
13
31%
|
| TR TEAEs → DC of Trebananib, Serious |
4
9.3%
|
11
26.2%
|
| TR TEAEs → DC of Trebananib, Non-Serious |
2
4.7%
|
2
4.8%
|
| TR TEAEs → DC of Sunitinib |
8
18.6%
|
15
35.7%
|
| TR TEAEs → DC of Sunitinib, Serious |
4
9.3%
|
11
26.2%
|
| TR TEAEs → DC of Sunitinib, Non-Serious |
4
9.3%
|
5
11.9%
|
| TR TEAEs → DC of All Treatment |
5
11.6%
|
13
31%
|
| TR TEAEs → DC of All Treatment, Serious |
4
9.3%
|
11
26.2%
|
| TR TEAEs → DC of All Treatment, Non-Serious |
1
2.3%
|
2
4.8%
|
| Trebananib-Related (TrR) TEAEs, All |
34
79.1%
|
39
92.9%
|
| TrR TEAEs, Grade ≥ 3 |
17
39.5%
|
19
45.2%
|
| TrR TEAEs, Grade ≥ 4 |
1
2.3%
|
4
9.5%
|
| TrR TEAEs, Fatal AEs |
0
0%
|
1
2.4%
|
| TrR TEAEs, SAEs |
10
23.3%
|
15
35.7%
|
| TrR TEAEs → DC of Trebananib |
6
14%
|
13
31%
|
| TrR TEAEs → DC of Trebananib, Serious |
4
9.3%
|
11
26.2%
|
| TrR TEAEs → DC of Trebananib, Non-Serious |
2
4.7%
|
2
4.8%
|
| TrR TEAEs → DC of Sunitinib |
6
14%
|
13
31%
|
| TrR TEAEs → DC of Sunitinib, Serious |
4
9.3%
|
11
26.2%
|
| TrR TEAEs → DC of Sunitinib, Non-Serious |
2
4.7%
|
3
7.1%
|
| TrR TEAEs → DC of All Treatment |
5
11.6%
|
13
31%
|
| TrR TEAEs → DC of All Treatment, Serious |
4
9.3%
|
11
26.2%
|
| TrR TEAEs → DC of All Treatment, Non-Serious |
1
2.3%
|
2
4.8%
|
| Sunitinib-Related (SR) TEAEs, All |
43
100%
|
42
100%
|
| SR TEAEs, Grade ≥ 3 |
25
58.1%
|
31
73.8%
|
| SR TEAEs, Grade ≥ 4 |
2
4.7%
|
5
11.9%
|
| SR TEAEs, Fatal AEs |
0
0%
|
1
2.4%
|
| SR TEAEs, SAEs |
9
20.9%
|
15
35.7%
|
| SR TEAEs → DC of Trebananib |
4
9.3%
|
11
26.2%
|
| SR TEAEs → DC of Trebananib, Serious |
3
7%
|
10
23.8%
|
| SR TEAEs → DC of Trebananib, Non-Serious |
1
2.3%
|
1
2.4%
|
| SR TEAEs → DC Sunitinib |
7
16.3%
|
13
31%
|
| SR TEAEs → DC of Sunitinib, Serious |
3
7%
|
10
23.8%
|
| SR TEAEs → DC of Sunitinib, Non-Serious |
4
9.3%
|
4
9.5%
|
| SR TEAEs → DC of All Treatment |
4
9.3%
|
11
26.2%
|
| SR TEAEs → DC of All Treatment, Serious |
3
7%
|
10
23.8%
|
| SR TEAEs → DC of All Treatment, Non-Serious |
1
2.3%
|
1
2.4%
|
| Title | Number of Participants With Dose Delays Due to Adverse Events |
|---|---|
| Description | A trebananib dose was considered delayed if it was administered 11 or more days from the previous trebananib infusion. A sunitinib dose was considered delayed if it was administered 3 or more days from the previous dose, except during holidays. |
| Time Frame | Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| Trebananib Dose Delays |
26
60.5%
|
28
66.7%
|
| Sunitinib Dose Delays |
29
67.4%
|
27
64.3%
|
| Title | Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose |
|---|---|
| Description | Participants who had a sunitinib dose modification within 12 weeks from their first dose due to adverse event, laboratory toxicity, or laboratory toxicity and adverse event. |
| Time Frame | first 12 weeks of study treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| Any Dose Modification (DM) |
25
58.1%
|
24
57.1%
|
| DM Due to Adverse Event |
20
46.5%
|
18
42.9%
|
| DM Due to Laboratory Toxicity |
4
9.3%
|
4
9.5%
|
| DM Due to Laboratory Toxicity and Adverse Event |
1
2.3%
|
2
4.8%
|
| Title | Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values |
|---|---|
| Description | Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death). |
| Time Frame | From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Aanalysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| Alanine Aminotransferase, Above Normal (AN) |
3
7%
|
2
4.8%
|
| Albumin, Below Normal (BN) |
1
2.3%
|
1
2.4%
|
| Alkaline Phosphatase, AN |
0
0%
|
2
4.8%
|
| Amylase, AN |
2
4.7%
|
5
11.9%
|
| Aspartate Aminotransferase, AN |
2
4.7%
|
2
4.8%
|
| Glucose, AN |
1
2.3%
|
3
7.1%
|
| Glucose, BN |
1
2.3%
|
0
0%
|
| Lipase, AN |
5
11.6%
|
7
16.7%
|
| Magnesium, BN |
0
0%
|
1
2.4%
|
| Phosphorus, BN |
3
7%
|
4
9.5%
|
| Potassium, BN |
2
4.7%
|
2
4.8%
|
| Sodium, BN |
1
2.3%
|
4
9.5%
|
| Total Bilirubin, AN |
0
0%
|
2
4.8%
|
| Absolute Neutrophil Count, BN |
3
7%
|
5
11.9%
|
| Hemoglobin, BN |
1
2.3%
|
3
7.1%
|
| Lymphocytes, BN |
6
14%
|
3
7.1%
|
| Partial Thromboplastin Time, AN |
1
2.3%
|
1
2.4%
|
| Platelets, BN |
3
7%
|
2
4.8%
|
| Total Neutrophils, BN |
3
7%
|
5
11.9%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) per modified Response Evaluation Criteria in Solid Tumor (RECIST) criteria (responder). A confirmed CR requires 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. All participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non responders. |
| Time Frame | 48 months after last subject enrolled (LSE) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 41 |
| Number (80% Confidence Interval) [percentage of participants] |
58.1
135.1%
|
63.4
151%
|
| Title | Kaplan-Meier Estimate: Duration of Response (DOR) |
|---|---|
| Description | DOR was calculated as the time from the first confirmed objective response to first observed disease progression per modified RECIST v. 1.0 criteria or death due to any cause. DOR was calculated only for participants who had an objective response. Objective response was defined as either a confirmed CR or PR per modified RECIST criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR required 2 consecutive assessments at least 28 days apart of PR or CR. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable radiographical disease assessment date. |
| Time Frame | 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with an objective response. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 25 | 26 |
| Median (80% Confidence Interval) [months] |
18.0
|
18.4
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | DCR was defined as the percentage of participants with confirmed CR or PR or stable disease (SD), as defined by modified RECIST v1.0 criteria. A confirmed CR required 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. CR or PR was confirmed at least 28 days after the criteria for response were first met. A response assessment of PR or CR that was not subsequently confirmed at least 4 weeks later were included as SD. |
| Time Frame | 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 41 |
| Number (80% Confidence Interval) [percentage of participants] |
72.1
167.7%
|
75.6
180%
|
| Title | Kaplan-Meier Estimate: Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from enrollment date to date of disease progression (ie, radiographic progression) per modified RECIST v 1.0 criteria or death. Radiological imaging to assess disease status was performed until participants developed disease progression. Events of radiographic progression per modified RECIST 1.0 that occurred after initiation of subsequent anticancer therapy were not considered PFS events. Deaths occurring after initiation of subsequent anticancer therapy were considered PFS events. Participants not meeting criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. |
| Time Frame | 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| Median (80% Confidence Interval) [months] |
13.9
|
16.5
|
| Title | Kaplan-Meier Estimate: Overall Survival (OS) |
|---|---|
| Description | The time from enrollment date to date of death. Participants who had not died by the analysis data cutoff date were censored at their last contact date. |
| Time Frame | 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 43 | 42 |
| Median (80% Confidence Interval) [months] |
36.0
|
38.7
|
| Title | Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir |
|---|---|
| Description | Change in tumor burden was evaluated by the maximum percent reduction from baseline in the SLD of target lesions. |
| Time Frame | Baseline, 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with baseline measureable disease and non-missing baseline and post-baseline data. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 41 | 40 |
| Mean (80% Confidence Interval) [percent reduction in SLD] |
-36.0
|
-41.8
|
| Title | Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time |
|---|---|
| Description | |
| Time Frame | Pre-infusion and up to 10 minutes post-infusion on Weeks 1, 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 38 | 41 |
| Week 1 |
222
|
297
|
| Week 4 |
285
|
377
|
| Week 7 |
260
|
377
|
| Week 10 |
257
|
476
|
| Week 13 |
219
|
385
|
| Week 22 |
249
|
417
|
| Week 34 |
240
|
387
|
| Week 46 |
221
|
349
|
| Week 58 |
229
|
|
| Week 70 |
185
|
|
| Week 82 |
223
|
|
| Week 94 |
270
|
|
| Week 106 |
289
|
|
| Safety Follow-Up |
3.46
|
8.26
|
| Title | Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time |
|---|---|
| Description | |
| Time Frame | Pre-infusion on Weeks 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 38 | 29 |
| Week 4 |
20.4
|
27.3
|
| Week 7 |
30.1
|
42.0
|
| Week 10 |
23.3
|
32.2
|
| Week 13 |
26.1
|
43.2
|
| Week 22 |
19.9
|
46.2
|
| Week 34 |
24.1
|
35.9
|
| Week 46 |
23.2
|
30.5
|
| Week 58 |
27.9
|
|
| Week 70 |
26.2
|
|
| Week 82 |
22.5
|
|
| Week 94 |
25.9
|
|
| Week 106 |
19.3
|
|
| Safety Follow-Up |
3.46
|
8.26
|
| Title | Pharmacokinetic Parameter: Cmin for Sunitinib Over Time |
|---|---|
| Description | |
| Time Frame | Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. Per protocol, this outcome measure evaluated a sub-group of participants at selected sites outside of Europe. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 9 | 7 |
| Week 4 |
58.6
|
70.6
|
| Week 7 |
0.763
|
1.65
|
| Week 10 |
66.1
|
64.7
|
| Week 16 |
65.8
|
73.1
|
| Week 22 |
49.0
|
41.2
|
| Week 34 |
50.2
|
34.8
|
| Week 46 |
59.5
|
33.5
|
| Week 58 |
87.0
|
|
| Week 70 |
56.4
|
|
| Week 82 |
65.9
|
|
| Week 94 |
64.2
|
|
| Week 106 |
83.5
|
|
| Safety Follow-Up |
NA
|
| Title | Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time |
|---|---|
| Description | |
| Time Frame | Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics Analysis Set: participants with evaluable concentration data at given time point. Per protocol, this outcome measure evaluated a sub-group of participants at selected sites outside of Europe. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 9 | 7 |
| Week 4 |
22.8
|
29.2
|
| Week 7 |
1.21
|
1.71
|
| Week 10 |
19.2
|
21.5
|
| Week 16 |
19.3
|
22.0
|
| Week 22 |
12.7
|
18.7
|
| Week 34 |
18.3
|
15.0
|
| Week 46 |
15.0
|
10.6
|
| Week 58 |
25.7
|
|
| Week 70 |
22.4
|
|
| Week 82 |
25.4
|
|
| Week 94 |
22.1
|
|
| Week 106 |
32.4
|
|
| Safety Follow-Up |
0.138
|
| Title | Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline |
|---|---|
| Description | Transient positive results were defined as a positive post-baseline result followed by a negative result at the participant's last time point tested within the study period. |
| Time Frame | 48 months after LSE |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who received at least 1 dose of trebananib and 1 dose of sunitinib. Participants with a post-baseline result and a negative result or no result at baseline. |
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib |
|---|---|---|
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off |
| Measure Participants | 41 | 41 |
| Binding Antibody Positive Post-Baseline (PBL) |
0
0%
|
0
0%
|
| Binding Antibody Positive PBL, Transient |
0
0%
|
0
0%
|
| Neutralizing Antibody Positive PBL |
0
0%
|
0
0%
|
| Neutralizing Antibody Positive PBL, Transient |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. Other adverse events shows non-serious occurrences of adverse event that exceed the indicated frequency threshold. | |||
| Arm/Group Title | Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib | ||
| Arm/Group Description | Trebananib 10 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off | ||
All Cause Mortality |
||||
| Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/43 (39.5%) | 26/42 (61.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/43 (2.3%) | 0/42 (0%) | ||
| Febrile bone marrow aplasia | 0/43 (0%) | 1/42 (2.4%) | ||
| Thrombocytopenia | 1/43 (2.3%) | 0/42 (0%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/43 (0%) | 1/42 (2.4%) | ||
| Atrial fibrillation | 1/43 (2.3%) | 0/42 (0%) | ||
| Myocardial infarction | 0/43 (0%) | 1/42 (2.4%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 0/43 (0%) | 1/42 (2.4%) | ||
| Eye disorders | ||||
| Glaucoma | 0/43 (0%) | 1/42 (2.4%) | ||
| Papilloedema | 1/43 (2.3%) | 0/42 (0%) | ||
| Uveitis | 1/43 (2.3%) | 0/42 (0%) | ||
| Vision blurred | 0/43 (0%) | 1/42 (2.4%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/43 (4.7%) | 0/42 (0%) | ||
| Colitis | 1/43 (2.3%) | 0/42 (0%) | ||
| Colitis ischaemic | 0/43 (0%) | 1/42 (2.4%) | ||
| Diarrhoea | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Duodenal ulcer | 0/43 (0%) | 1/42 (2.4%) | ||
| Dysphagia | 0/43 (0%) | 1/42 (2.4%) | ||
| Gastrooesophageal reflux disease | 1/43 (2.3%) | 0/42 (0%) | ||
| Ileus paralytic | 0/43 (0%) | 1/42 (2.4%) | ||
| Nausea | 1/43 (2.3%) | 0/42 (0%) | ||
| Rectourethral fistula | 0/43 (0%) | 1/42 (2.4%) | ||
| Small intestinal obstruction | 0/43 (0%) | 1/42 (2.4%) | ||
| Vomiting | 0/43 (0%) | 1/42 (2.4%) | ||
| General disorders | ||||
| Asthenia | 0/43 (0%) | 3/42 (7.1%) | ||
| Chest discomfort | 0/43 (0%) | 1/42 (2.4%) | ||
| Chest pain | 1/43 (2.3%) | 1/42 (2.4%) | ||
| Fatigue | 2/43 (4.7%) | 2/42 (4.8%) | ||
| General physical health deterioration | 2/43 (4.7%) | 1/42 (2.4%) | ||
| Infusion site inflammation | 0/43 (0%) | 1/42 (2.4%) | ||
| Malaise | 2/43 (4.7%) | 0/42 (0%) | ||
| Mucosal inflammation | 0/43 (0%) | 1/42 (2.4%) | ||
| Oedema | 0/43 (0%) | 1/42 (2.4%) | ||
| Pyrexia | 0/43 (0%) | 3/42 (7.1%) | ||
| Swelling | 0/43 (0%) | 1/42 (2.4%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stenosis | 0/43 (0%) | 1/42 (2.4%) | ||
| Cholangitis | 0/43 (0%) | 1/42 (2.4%) | ||
| Cholecystitis | 0/43 (0%) | 2/42 (4.8%) | ||
| Cholecystitis acute | 0/43 (0%) | 1/42 (2.4%) | ||
| Cholecystitis chronic | 0/43 (0%) | 1/42 (2.4%) | ||
| Cholelithiasis | 1/43 (2.3%) | 1/42 (2.4%) | ||
| Hyperbilirubinaemia | 0/43 (0%) | 1/42 (2.4%) | ||
| Infections and infestations | ||||
| Anal abscess | 0/43 (0%) | 1/42 (2.4%) | ||
| Escherichia sepsis | 0/43 (0%) | 1/42 (2.4%) | ||
| Infection | 1/43 (2.3%) | 0/42 (0%) | ||
| Pneumonia | 1/43 (2.3%) | 0/42 (0%) | ||
| Sepsis | 0/43 (0%) | 1/42 (2.4%) | ||
| Urinary tract infection | 1/43 (2.3%) | 1/42 (2.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Humerus fracture | 0/43 (0%) | 1/42 (2.4%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/43 (2.3%) | 2/42 (4.8%) | ||
| Diabetes mellitus inadequate control | 0/43 (0%) | 1/42 (2.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/43 (2.3%) | 0/42 (0%) | ||
| Bone pain | 0/43 (0%) | 1/42 (2.4%) | ||
| Muscular weakness | 0/43 (0%) | 1/42 (2.4%) | ||
| Osteonecrosis of jaw | 0/43 (0%) | 1/42 (2.4%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Renal cancer | 1/43 (2.3%) | 0/42 (0%) | ||
| Renal cell carcinoma | 1/43 (2.3%) | 0/42 (0%) | ||
| Nervous system disorders | ||||
| Brain hypoxia | 0/43 (0%) | 1/42 (2.4%) | ||
| Loss of consciousness | 1/43 (2.3%) | 0/42 (0%) | ||
| Migraine with aura | 1/43 (2.3%) | 0/42 (0%) | ||
| Monoplegia | 0/43 (0%) | 1/42 (2.4%) | ||
| Presyncope | 1/43 (2.3%) | 0/42 (0%) | ||
| Syncope | 0/43 (0%) | 1/42 (2.4%) | ||
| Product Issues | ||||
| Device occlusion | 0/43 (0%) | 2/42 (4.8%) | ||
| Psychiatric disorders | ||||
| Confusional state | 0/43 (0%) | 1/42 (2.4%) | ||
| Mental status changes | 0/43 (0%) | 1/42 (2.4%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/43 (2.3%) | 0/42 (0%) | ||
| Renal failure | 0/43 (0%) | 1/42 (2.4%) | ||
| Urinary retention | 0/43 (0%) | 1/42 (2.4%) | ||
| Reproductive system and breast disorders | ||||
| Pelvic pain | 0/43 (0%) | 1/42 (2.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 0/43 (0%) | 1/42 (2.4%) | ||
| Dyspnoea | 0/43 (0%) | 1/42 (2.4%) | ||
| Hypoxia | 0/43 (0%) | 1/42 (2.4%) | ||
| Pleural effusion | 1/43 (2.3%) | 1/42 (2.4%) | ||
| Pneumonitis | 0/43 (0%) | 1/42 (2.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin ulcer | 1/43 (2.3%) | 0/42 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/43 (0%) | 1/42 (2.4%) | ||
| Hypertension | 2/43 (4.7%) | 0/42 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Trebananib 10 mg/kg + Sunitinib | Trebananib 15 mg/kg + Sunitinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 43/43 (100%) | 42/42 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/43 (11.6%) | 7/42 (16.7%) | ||
| Leukopenia | 2/43 (4.7%) | 3/42 (7.1%) | ||
| Neutropenia | 5/43 (11.6%) | 4/42 (9.5%) | ||
| Thrombocytopenia | 14/43 (32.6%) | 11/42 (26.2%) | ||
| Cardiac disorders | ||||
| Pericardial effusion | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Ear and labyrinth disorders | ||||
| Hypoacusis | 3/43 (7%) | 1/42 (2.4%) | ||
| Tinnitus | 3/43 (7%) | 0/42 (0%) | ||
| Vertigo | 1/43 (2.3%) | 4/42 (9.5%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 2/43 (4.7%) | 5/42 (11.9%) | ||
| Hypothyroidism | 21/43 (48.8%) | 18/42 (42.9%) | ||
| Eye disorders | ||||
| Eyelid oedema | 10/43 (23.3%) | 8/42 (19%) | ||
| Glaucoma | 3/43 (7%) | 0/42 (0%) | ||
| Lacrimation increased | 13/43 (30.2%) | 12/42 (28.6%) | ||
| Periorbital oedema | 5/43 (11.6%) | 8/42 (19%) | ||
| Visual acuity reduced | 3/43 (7%) | 0/42 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 3/43 (7%) | 2/42 (4.8%) | ||
| Abdominal distension | 3/43 (7%) | 0/42 (0%) | ||
| Abdominal pain | 13/43 (30.2%) | 15/42 (35.7%) | ||
| Abdominal pain upper | 14/43 (32.6%) | 9/42 (21.4%) | ||
| Aphthous ulcer | 9/43 (20.9%) | 6/42 (14.3%) | ||
| Ascites | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Constipation | 13/43 (30.2%) | 8/42 (19%) | ||
| Diarrhoea | 33/43 (76.7%) | 32/42 (76.2%) | ||
| Dry mouth | 6/43 (14%) | 3/42 (7.1%) | ||
| Dyspepsia | 16/43 (37.2%) | 10/42 (23.8%) | ||
| Dysphagia | 1/43 (2.3%) | 5/42 (11.9%) | ||
| Flatulence | 2/43 (4.7%) | 5/42 (11.9%) | ||
| Gastrooesophageal reflux disease | 8/43 (18.6%) | 3/42 (7.1%) | ||
| Gingival pain | 0/43 (0%) | 3/42 (7.1%) | ||
| Haemorrhoids | 3/43 (7%) | 5/42 (11.9%) | ||
| Nausea | 22/43 (51.2%) | 19/42 (45.2%) | ||
| Oesophagitis | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Stomatitis | 4/43 (9.3%) | 8/42 (19%) | ||
| Vomiting | 17/43 (39.5%) | 13/42 (31%) | ||
| General disorders | ||||
| Asthenia | 16/43 (37.2%) | 20/42 (47.6%) | ||
| Catheter site pain | 3/43 (7%) | 0/42 (0%) | ||
| Chest pain | 1/43 (2.3%) | 5/42 (11.9%) | ||
| Chills | 3/43 (7%) | 6/42 (14.3%) | ||
| Face oedema | 15/43 (34.9%) | 21/42 (50%) | ||
| Fatigue | 16/43 (37.2%) | 14/42 (33.3%) | ||
| Generalised oedema | 4/43 (9.3%) | 3/42 (7.1%) | ||
| Influenza like illness | 2/43 (4.7%) | 3/42 (7.1%) | ||
| Localised oedema | 6/43 (14%) | 3/42 (7.1%) | ||
| Malaise | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Mucosal dryness | 3/43 (7%) | 0/42 (0%) | ||
| Mucosal inflammation | 22/43 (51.2%) | 25/42 (59.5%) | ||
| Oedema peripheral | 24/43 (55.8%) | 24/42 (57.1%) | ||
| Pyrexia | 4/43 (9.3%) | 3/42 (7.1%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Infections and infestations | ||||
| Bronchitis | 3/43 (7%) | 3/42 (7.1%) | ||
| Conjunctivitis | 4/43 (9.3%) | 4/42 (9.5%) | ||
| Cystitis | 0/43 (0%) | 3/42 (7.1%) | ||
| Ear infection | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Gastroenteritis | 6/43 (14%) | 1/42 (2.4%) | ||
| Influenza | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Laryngitis | 2/43 (4.7%) | 3/42 (7.1%) | ||
| Nasopharyngitis | 4/43 (9.3%) | 2/42 (4.8%) | ||
| Oral herpes | 3/43 (7%) | 2/42 (4.8%) | ||
| Pharyngitis | 0/43 (0%) | 3/42 (7.1%) | ||
| Rhinitis | 8/43 (18.6%) | 4/42 (9.5%) | ||
| Sinusitis | 2/43 (4.7%) | 3/42 (7.1%) | ||
| Tooth abscess | 5/43 (11.6%) | 2/42 (4.8%) | ||
| Upper respiratory tract infection | 5/43 (11.6%) | 7/42 (16.7%) | ||
| Urinary tract infection | 1/43 (2.3%) | 4/42 (9.5%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 4/43 (9.3%) | 0/42 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 3/43 (7%) | 3/42 (7.1%) | ||
| Amylase increased | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Aspartate aminotransferase increased | 3/43 (7%) | 2/42 (4.8%) | ||
| Blood creatinine increased | 3/43 (7%) | 3/42 (7.1%) | ||
| Lipase increased | 1/43 (2.3%) | 5/42 (11.9%) | ||
| Weight decreased | 5/43 (11.6%) | 4/42 (9.5%) | ||
| Weight increased | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 17/43 (39.5%) | 24/42 (57.1%) | ||
| Dehydration | 5/43 (11.6%) | 3/42 (7.1%) | ||
| Hyperglycaemia | 0/43 (0%) | 3/42 (7.1%) | ||
| Hypoalbuminaemia | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Hypokalaemia | 4/43 (9.3%) | 3/42 (7.1%) | ||
| Hypophosphataemia | 3/43 (7%) | 8/42 (19%) | ||
| Obesity | 0/43 (0%) | 3/42 (7.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 17/43 (39.5%) | 10/42 (23.8%) | ||
| Back pain | 12/43 (27.9%) | 5/42 (11.9%) | ||
| Bone pain | 7/43 (16.3%) | 4/42 (9.5%) | ||
| Groin pain | 3/43 (7%) | 2/42 (4.8%) | ||
| Muscle spasms | 6/43 (14%) | 4/42 (9.5%) | ||
| Muscular weakness | 4/43 (9.3%) | 5/42 (11.9%) | ||
| Musculoskeletal pain | 7/43 (16.3%) | 7/42 (16.7%) | ||
| Myalgia | 6/43 (14%) | 6/42 (14.3%) | ||
| Pain in extremity | 10/43 (23.3%) | 5/42 (11.9%) | ||
| Spinal pain | 3/43 (7%) | 1/42 (2.4%) | ||
| Nervous system disorders | ||||
| Ageusia | 5/43 (11.6%) | 3/42 (7.1%) | ||
| Dizziness | 10/43 (23.3%) | 6/42 (14.3%) | ||
| Dysgeusia | 6/43 (14%) | 3/42 (7.1%) | ||
| Formication | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Headache | 13/43 (30.2%) | 6/42 (14.3%) | ||
| Neuropathy peripheral | 3/43 (7%) | 4/42 (9.5%) | ||
| Paraesthesia | 3/43 (7%) | 3/42 (7.1%) | ||
| Presyncope | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Sciatica | 3/43 (7%) | 1/42 (2.4%) | ||
| Syncope | 1/43 (2.3%) | 3/42 (7.1%) | ||
| Taste disorder | 14/43 (32.6%) | 10/42 (23.8%) | ||
| Psychiatric disorders | ||||
| Anxiety | 4/43 (9.3%) | 2/42 (4.8%) | ||
| Depression | 4/43 (9.3%) | 3/42 (7.1%) | ||
| Insomnia | 8/43 (18.6%) | 5/42 (11.9%) | ||
| Renal and urinary disorders | ||||
| Dysuria | 3/43 (7%) | 5/42 (11.9%) | ||
| Proteinuria | 2/43 (4.7%) | 6/42 (14.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 13/43 (30.2%) | 12/42 (28.6%) | ||
| Dysphonia | 7/43 (16.3%) | 2/42 (4.8%) | ||
| Dyspnoea | 7/43 (16.3%) | 8/42 (19%) | ||
| Dyspnoea exertional | 3/43 (7%) | 4/42 (9.5%) | ||
| Epistaxis | 12/43 (27.9%) | 6/42 (14.3%) | ||
| Hiccups | 3/43 (7%) | 1/42 (2.4%) | ||
| Nasal dryness | 3/43 (7%) | 0/42 (0%) | ||
| Oropharyngeal pain | 7/43 (16.3%) | 5/42 (11.9%) | ||
| Pleural effusion | 5/43 (11.6%) | 3/42 (7.1%) | ||
| Rhinorrhoea | 3/43 (7%) | 2/42 (4.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 18/43 (41.9%) | 6/42 (14.3%) | ||
| Erythema | 6/43 (14%) | 2/42 (4.8%) | ||
| Hair colour changes | 5/43 (11.6%) | 3/42 (7.1%) | ||
| Hyperhidrosis | 3/43 (7%) | 1/42 (2.4%) | ||
| Hyperkeratosis | 4/43 (9.3%) | 4/42 (9.5%) | ||
| Nail disorder | 4/43 (9.3%) | 1/42 (2.4%) | ||
| Palmar-plantar erythrodysaesthesia syndrome | 21/43 (48.8%) | 18/42 (42.9%) | ||
| Pruritus | 5/43 (11.6%) | 4/42 (9.5%) | ||
| Rash | 9/43 (20.9%) | 9/42 (21.4%) | ||
| Skin discolouration | 4/43 (9.3%) | 2/42 (4.8%) | ||
| Skin disorder | 3/43 (7%) | 0/42 (0%) | ||
| Skin exfoliation | 4/43 (9.3%) | 3/42 (7.1%) | ||
| Skin toxicity | 4/43 (9.3%) | 4/42 (9.5%) | ||
| Yellow skin | 4/43 (9.3%) | 5/42 (11.9%) | ||
| Vascular disorders | ||||
| Hypertension | 26/43 (60.5%) | 23/42 (54.8%) | ||
| Hypotension | 3/43 (7%) | 7/42 (16.7%) | ||
| Pallor | 1/43 (2.3%) | 3/42 (7.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT00853372
Other Study ID Numbers:
- 20080579
First Posted:
Mar 2, 2009
Last Update Posted:
Jul 1, 2020
Last Verified:
May 1, 2020