- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02525536
A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Trebananib (AMG 386 ) in Adult Japanese Participants With Advanced Solid Tumors
A Phase 1, Open-Label, Dose Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of Trebananib (AMG 386) in Adult Japanese Patients With Advanced Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The drug being tested in this study is called trebananib (AMG 386). Trebananib (AMG 386) is being tested to treat people with advanced solid tumors.
This study will look at the safety, tolerability and pharmacokinetic (PK) profile of trebananib and response to treatment.
The study will enroll approximately 18 participants. Once enrolled, participants will be assigned sequentially into 1 of the 3 cohorts:
- Trebananib 3 milligram/kilogram (mg/kg),
- Trebananib 10 mg/kg,
- Trebananib 30 mg/kg.
All participants will receive trebananib via 60 minute intravenous infusion. This study will be conducted in Japan. The overall time to participate in this study is 14 weeks or more. Participants will attend the end-of-treatment visit 28 days after the last dose of study drug.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Trebananib 3 mg/kg
Trebananib (AMG 386) 3 milligram/kilogram (mg/kg), 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
|
Trebananib (AMG 386) 3 mg/kg, intravenous infusion.
|
Experimental: Trebananib 10 mg/kg
Trebananib (AMG 386) 10 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
|
Trebananib (AMG 386) 10 mg/kg, intravenous infusion.
|
Experimental: Trebananib 30 mg/kg
Trebananib (AMG 386) 30 mg/kg, 60-minute infusion, intravenously once weekly on Days 1, 8, 15 and 22 and thereafter once weekly starting from Day 36 (Week 6) until intolerance to investigational product, progressive disease, consent withdrawn, or lost to follow-up (up to approximately 249 weeks).
|
Trebananib (AMG 386) 30 mg/kg, intravenous infusion.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: Day 1 up to Day 28
|
DLT is defined as any treatment-related, grade 4 or higher hematologic or grade 3 or higher non-hematologic toxicity (according to the Common Terminology Criteria for Adverse Events [CTCAE] version 3.0; hematologic toxicity means any toxicities which are categorized in blood/bone marrow category of CTCAE), except for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and infusion reaction, occurred during the first 28 days after the initial administration (before examination on Study Day 29).
DLT also includes AST or ALT: >10*upper limit of normal (ULN) international units per liter (IU/L).
|
Day 1 up to Day 28
|
Number of Participants Reporting One or More Treatment-emergent Adverse Events (AEs) and Serious Adverse Event (SAEs)
Time Frame: Baseline up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Treatment emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
|
Baseline up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Number of Participants With Significant Change From Baseline in Electrocardiogram (ECG)
Time Frame: Week 1: predose, 1, 6 hours after end of infusion, Week 4: predose, 1 hour after end of infusion, Week 8, 16: predose, thereafter predose of every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Change relative to baseline in electrocardiogram measured throughout study.
Significant change in ECG observed at any time point was summarized and reported.
|
Week 1: predose, 1, 6 hours after end of infusion, Week 4: predose, 1 hour after end of infusion, Week 8, 16: predose, thereafter predose of every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after infusion end, Week 2, 3, 4: predose and 1 hour after infusion end, thereafter predose of every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)
|
Vital signs included body temperature, diastolic and systolic blood pressure, and pulse (beats per minutes).
clinically significant change in vital signs observed at any time point was summarized and reported.
|
Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after infusion end, Week 2, 3, 4: predose and 1 hour after infusion end, thereafter predose of every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)
|
Number of Participants With Abnormal Laboratory Values
Time Frame: Week 1: predose, 24, 48 and 96 hours after infusion end, Week 2 and 3: predose, Week 4: predose and 1 hour after infusion end, thereafter every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)
|
The number of participants with any abnormal standard safety laboratory values collected throughout study.
Parameters assessed were hematology, chemistry, coagulation and urinalysis.
Abnormal laboratory values observed at any time point was summarized and reported.
|
Week 1: predose, 24, 48 and 96 hours after infusion end, Week 2 and 3: predose, Week 4: predose and 1 hour after infusion end, thereafter every 4 weeks starting from Week 8 up to 4 weeks after the last dose of study drug (last dose=Week 249)
|
Cmax: Maximum Observed Serum Concentration for AMG 386 After Week 1 Dose
Time Frame: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.
|
Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
Cmax: Maximum Observed Serum Concentration for AMG 386 After Week 4 Dose
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Cmax is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.
|
Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for AMG 386 After Week 1 Dose
Time Frame: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.
|
Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for AMG 386 After Week 4 Dose
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.
|
Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
AUC (0-tau): Area Under the Serum Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for AMG 386 After Week 1 Dose
Time Frame: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
AUC (0-tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen).
|
Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose
|
AUC (0-tau): Area Under the Serum Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for AMG 386 After Week 4 Dose
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion
|
AUC (0-tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen).
|
Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion
|
Cmin: Minimum Observed Serum Trough Concentration for AMG 386 After Week 1 Dose
Time Frame: Week 2: predose
|
Cmin was the observed serum concentration at 168 hours postdose.
|
Week 2: predose
|
Cmin: Minimum Observed Serum Trough Concentration for AMG 386 After Week 4 Dose
Time Frame: Week 4: 168 hours after end of infusion
|
Cmin was the observed serum concentration at 168 hours postdose.
|
Week 4: 168 hours after end of infusion
|
Vss: Volume of Distribution at Steady State for AMG 386
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Vss is the apparent volume of distribution at steady-state, estimated as: Vss = MRTinf *CLss, where MRTinf is mean residence time of drug extrapolated to infinity and CLss is the systemic clearance at the steady state.
Vss was normalized to participant's body weight.
|
Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Terminal Phase Elimination Half-life (T1/2) for AMG 386
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
|
Week 4: predose, 1, 2, 6, 24, 48, 96, 168 and 264 hours after end of infusion
|
Systemic Clearance at Steady State (CLss) for AMG 386
Time Frame: Week 4: predose, 1, 2, 6, 24, 48, 96 and 168 hours after end of infusion
|
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Systemic clearance at steady state (CLss) was calculated as the ratio of dose administered to AUC (0 - tau), where AUC (0 - tau) is the area under the serum concentration-time curve during a dosing interval, where tau is the length of the dosing interval (168 hours for once weekly regimen).
CLss was normalized to participant's body weight.
|
Week 4: predose, 1, 2, 6, 24, 48, 96 and 168 hours after end of infusion
|
Accumulation Ratio (AR) for AMG 386
Time Frame: Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose, Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion
|
Accumulation ratio (AR) was calculated by dividing the individual AUC (0-tau) value at Week 4 by the corresponding individual AUC (0-tau) value at Week 1.
|
Week 1: predose, 1, 2, 6, 24, 48 and 96 hours after end of infusion, Week 2: predose, Week 4: predose, 1, 2, 6, 24, 48, 96, and 168 hours after end of infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Best Overall Response
Time Frame: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Best overall response for a participant is the best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria.
Complete Response (CR): disappearance of all target lesions, non-target lesions and normalization of tumor marker level.
Partial Response (PR): at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the baseline smallest sum of longest diameter; persistence of 1 or more non-target lesion(s) or maintenance of tumor marker level above the normal limits.
PD: at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions.
|
Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Percentage of Participants With Objective Response
Time Frame: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Objective response rate defined as the rate of participants with CR or PR based on RECIST 1.0 criteria.
CR: disappearance of all target lesions, non-target lesions and normalization of tumor marker level.
PR: at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
|
Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Time to Progression (TTP)
Time Frame: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
TTP is defined as the time from the date of first administration of study treatment to the date of first documentation of PD or death caused by progression.
For participants who did not have a documented PD or died owing to causes other than progression, TTP was censored at the time of last response assessment.
PD is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions.
|
Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Percent Change From Baseline to Post-baseline in the Sum of the Longest Diameters of Tumor
Time Frame: Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
The percent change from baseline to post-baseline is the largest percent reduction from baseline among all post-dose measures of the sum of the longest diameter of the tumor burden.
|
Baseline, assessed every 8 weeks up to 4 weeks after the last dose of study drug, where last dose was given up to Week 249
|
Number of Participant With Anti-AMG 386 Antibody
Time Frame: Week 1: predose,1,2,6,24,48 and 98 hours after infusion end, Week 3: predose, Week 4: predose, 1,2,6,24,48,96,168 and 264 hours after infusion end, thereafter predose every 4 weeks starting from Week 8 up to 8 weeks after last dose (last dose=Week 249)
|
The immunogenicity of AMG 386 was evaluated with an immunoassay that detects anti-AMG 386 binding antibodies.
Antibody formation reported at any of the time points was summarized.
|
Week 1: predose,1,2,6,24,48 and 98 hours after infusion end, Week 3: predose, Week 4: predose, 1,2,6,24,48,96,168 and 264 hours after infusion end, thereafter predose every 4 weeks starting from Week 8 up to 8 weeks after last dose (last dose=Week 249)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20060212
- U1111-1170-0395 (Registry Identifier: WHO)
- JapicCTI-101161 (Registry Identifier: JapicCTI)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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