Back to resultsAMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib
Primary Purpose
Advanced Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sunitinib
Trebananib
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Renal Cell Carcinoma
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Trebananib 10 mg/kg + Sunitinib
Trebananib 15 mg/kg + Sunitinib
Arm 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
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)
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
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
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
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)
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)
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)
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)
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)
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
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
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time
Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00853372
Brief Title
AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
May 28, 2009 (Actual)
Primary Completion Date
August 8, 2011 (Actual)
Study Completion Date
June 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
85 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trebananib 10 mg/kg + Sunitinib
Arm Type
Experimental
Arm 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
Arm Title
Trebananib 15 mg/kg + Sunitinib
Arm Type
Experimental
Arm Description
Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Other Intervention Name(s)
SUTENT (oral multi-kinase inhibitor)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Trebananib
Other Intervention Name(s)
AMG 386, Angiogenesis inhibitor
Intervention Description
Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Primary Outcome Measure Information:
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.
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.
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
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.
Secondary Outcome Measure Information:
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)
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
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
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
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
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
Title
Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time
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)
Title
Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time
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)
Title
Pharmacokinetic Parameter: Cmin for Sunitinib Over Time
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)
Title
Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time
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)
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
IPD Sharing Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
IPD Sharing URL
https://www.amgen.com/datasharing
Citations:
PubMed Identifier
26304872
Citation
Atkins MB, Gravis G, Drosik K, Demkow T, Tomczak P, Wong SS, Michaelson MD, Choueiri TK, Wu B, Navale L, Warner D, Ravaud A. Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study. J Clin Oncol. 2015 Oct 20;33(30):3431-8. doi: 10.1200/JCO.2014.60.6012. Epub 2015 Aug 24.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib
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