Neoplasms, Advanced SolidPhase 1NCT02525536
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 study testing Trebananib 3 mg/kg, Trebananib 10 mg/kg and Trebananib 30 mg/kg in people with Neoplasms, Advanced Solid, run by Takeda.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetic (PK) profile of trebananib (AMG 386) after intravenous administration in adult Japanese participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 20 to 74 years
- Conditions the study is for
- Neoplasms, Advanced Solid
- What is being tested?
- Trebananib 3 mg/kg, Trebananib 10 mg/kg and Trebananib 30 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to May 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: 1. Histologically or cytologically documented and definitively diagnosed, advanced solid tumor that is refractory to standard treatment or for which no curative therapy is available. 2. Has Eastern Cooperative Oncology Group (ECOG) of 0 or 1 (within 2 weeks prior to enrollment). 3. Men or women, 20 to 74 years old at the time the written informed consent is obtained. 4. Those meeting the following laboratory criteria (within 2 weeks prior to enrollment): A. Hematological function, as follows: • Absolute neutrophil count >=1500 /microliter (mcL) (without granulocyte colony stimulating factor support within 2 weeks of enrollment). • Platelet count >=10*10^4 /mcL (without transfusion within 2 weeks of enrollment). • Hemoglobin >=9 grams per deciliter (g/dL) (without transfusion within 2 weeks of enrollment). B. Renal function, as follows: • Calculated creatinine clearance (CCr) >40 milliliter per minute (mL/min) according to the Cockcroft-Gault formula. • Urinary protein quantitative value of less than or equal to (<=) 30 mg/dL in urinalysis or <=1+ on dipstick, unless quantitative protein is <=1,000 mg in a 24 hour urine sample. C. Hepatic function, as follows: • AST <=2.5*ULN (if liver metastases are present, <=5*ULN). • ALT <=2.5*ULN (if liver metastases are present, <=5*ULN). • Alkaline phosphatase <=2.0*ULN (if bone or liver metastates present <=5*ULN). • Total bilirubin <=2.0*ULN. D. Hemostatic function, as follows: • Prothrombin time (PT) or activated partial thromboplastin time (APTT) <=1.5*ULN. E. ECG • Normal sinus rhythm (no clinical significant 12-lead ECG changes) 5. Life expectancy of 3 months, in the judgment of the investigator. Exclusion Criteria: 1. Has primary central nervous system (CNS) tumors, including any CNS lymphoma. 2. Has history of CNS metastases (including previously treated metastases) (The brain imaging test by CT or MRI will be performed at screening. If the imaging test was performed within 3 months prior to written informed consent, the result can be used to confirm the exclusion criterion.) 3. Has hematological malignancies. 4. Has unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE grade 0 or 1, or to levels specified in the inclusion/exclusion criteria with the exception of alopecia. 5. Has clinically significant cardiovascular disease within 1 year prior to enrollment, including myocardial infarction, unstable angina, New York Heart Association class 2 or greater heart failure, peripheral vascular disease, cerebrovascular accident, transient ischemic attack, or arrhythmias not controlled by outpatient medication. 6. Has uncontrolled hypertension [diastolic >90 millimeter of mercury [mmHg]; systolic >150 mmHg]. Participant on antihypertensive medication must meet these parameters on a stable antihypertensive. 7. Has history of arterial or venous (deep vein) thrombosis within 1 year before enrollment. 8. Has presence of ascites or pleural effusion requiring medical intervention (example, drainage.) 9. Has history of bleeding diathesis or clinically significant bleeding including hemoptysis within 6 months of enrollment. 10. Has non-healing wound, ulcer or fracture. 11. With head and neck cancer. 12. Has squamous cell tumor or lung cancer with large central (located adjacent to or within the hilum or mediastinum) tumor lesions >=3 centimeter (cm), regardless of histology. 13. Has positive test for human immunodeficiency virus infection. 14. Has positive test for hepatitis C virus infection (positive hepatitis C virus antibody [HCVAb] or hepatitis B infection (positive hepatitis B virus antigen [HBsAg] or positive hepatitis B virus antibody [HBcAb])). 15. Had major surgery (requiring general anesthesia) within 4 weeks before enrollment. 16. Has minor surgery, placement of central venous catheter, or fine needle aspiration within 7 days prior to enrollment. 17. Is unable to tolerate IV administration, in the judgment of the investigator. 18. Has prior anti-tumor therapies, defined as: •Treatment with tumor directed antibody therapy within 4 weeks prior to Study Day 1, with the exception of bevacizumab and other monoclonal antibodies with a half-life >10 days, which must be discontinued at least 8 weeks prior to Study Day 1. •Anti-cancer therapy including chemotherapy and retinoid therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin) before Study Day 1. •Hormonal anti-tumor therapy within 4 weeks before Study Day 1. Does not include hormones for non-cancer related conditions (example, insulin for diabetes, hormone replacement therapy). •Therapeutic or palliative radiation therapy within 4 weeks before Study Day 1 (participants must have resolution of any significant adverse effects from radiation therapy received prior to 2 weeks before Study Day 1). 19. Has any elective surgeries scheduled during their participation in the study. 20. Has prior radiation to abdomen. 21. Has concurrent or prior (within 4 weeks before Study Day 1) anticoagulation therapy excluding aspirin and anti-platelet agents. The concurrent use of low molecular weight heparin or low dose warfarin (<=1 mg daily) for prophylaxis against thrombosis is acceptable. 22. Has concurrent immunosuppressant therapy (cyclosporine, tacrolimus, or chronic treatment with prednisolone [> 5 mg daily]) within 4 weeks prior to Study Day 1. 23. Currently or previously treated with angiopoietin inhibitors, or inhibitors of Tie-1 or Tie-2 including, but not limited to, AMG 386, XL880, XL820. 24. Is enrolled in the clinical study for other investigational products or devices or within 4 weeks since the last administration at the enrollment. 25. Is pregnant (example, positive human choriogonadotropin [HCG] test) or breastfeeding. 26. Has a childbearing potential, or participant who has a partner of childbearing potential, who is not using adequate contraceptive precautions, and participant unwilling for 6 months after the last AMG 386 infusion. 27. Has any kind of disorder that compromises the ability of the participant to give written informed consent and/or comply with study procedures. 28. Has any co-morbid medical condition that would increase the risk of toxicity, in the judgement of the investigator or the sponsor. 29. The investigator has determined the participant has difficulties that would prevent the participant's ability to participate in the study. 30. Has a history of allergic reactions to bacterially produced proteins. 31. Has a history of severe drug hypersensitivity.
About this study
Official title: 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
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetic (PK) profile of trebananib (AMG 386) after intravenous administration in adult Japanese participants with advanced solid tumors.
Read the 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.
- Conditions
- Neoplasms, Advanced Solid
- Being tested
- Trebananib 3 mg/kg, Trebananib 10 mg/kg, Trebananib 30 mg/kg
- Keywords
- Drug Therapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trebananib 3 mg/kgDrug
Trebananib (AMG 386) 3 mg/kg, intravenous infusion.
Trebananib 10 mg/kgDrug
Trebananib (AMG 386) 10 mg/kg, intravenous infusion.
Trebananib 30 mg/kgDrug
Trebananib (AMG 386) 30 mg/kg, intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Trebananib 3 mg/kg | Experimental | 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). Receives: Drug: Trebananib 3 mg/kg |
| Trebananib 10 mg/kg | Experimental | 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). Receives: Drug: Trebananib 10 mg/kg |
| Trebananib 30 mg/kg | Experimental | 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). Receives: Drug: Trebananib 30 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicity (DLT)
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).
Measured: Day 1 up to Day 28
Number of Participants Reporting One or More Treatment-emergent Adverse Events (AEs) and Serious Adverse Event (SAEs)
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.
Measured: 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)
Change relative to baseline in electrocardiogram measured throughout study. Significant change in ECG observed at any time point was summarized and reported.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.
Measured: 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
Cmax is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.
Measured: 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
Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.
Measured: 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
Tmax is the time to reach the maximum serum concentration (Cmax), equal to time (hours) to Cmax.
Measured: 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
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).
Measured: 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
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).
Measured: 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
Cmin was the observed serum concentration at 168 hours postdose.
Measured: Week 2: predose
Cmin: Minimum Observed Serum Trough Concentration for AMG 386 After Week 4 Dose
Cmin was the observed serum concentration at 168 hours postdose.
Measured: Week 4: 168 hours after end of infusion
Vss: Volume of Distribution at Steady State for AMG 386
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.
Measured: 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
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Measured: 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
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.
Measured: Week 4: predose, 1, 2, 6, 24, 48, 96 and 168 hours after end of infusion
Accumulation Ratio (AR) for AMG 386
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.
Measured: 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 outcomes (5)
Number of Participants With Best Overall Response
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study startJun 2009
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, Advanced SolidStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525536
- Sponsor's protocol ID
- 20060212
- Other IDs
- U1111-1170-0395, JapicCTI-101161
- Status last verified
- Aug 2015
- First submitted
- 26 Jul 2015
- Last updated
- 22 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Doi T, Ohtsu A, Fuse N, Yoshino T, Tahara M, Shibayama K, Takubo T, Weinreich DM. Phase 1 study of trebananib (AMG 386), an angiogenesis targeting angiopoietin-1/2 antagonist, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jan;71(1):227-35. doi: 10.1007/s00280-012-2000-1. Epub 2012 Nov 3.
PubMed 23124648
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02525536
- Acronym / sponsor ID
- 20060212
- Conditions
- Neoplasms, Advanced Solid
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 22 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetic (PK) profile of trebananib (AMG 386) after intravenous administration in adult Japanese participants with advanced solid tumors.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Trebananib 3 mg/kg | Experimental | Drug: Trebananib 3 mg/kgTrebananib (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 10 mg/kg | Experimental | Drug: Trebananib 10 mg/kgTrebananib (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 30 mg/kg | Experimental | Drug: Trebananib 30 mg/kgTrebananib (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). |
Who may qualify
- Ages
- 20 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trebananib 3 mg/kgTrebananib (AMG 386) 3 mg/kg, intravenous infusion. | Drug | Trebananib 3 mg/kg |
| Trebananib 10 mg/kgTrebananib (AMG 386) 10 mg/kg, intravenous infusion. | Drug | Trebananib 10 mg/kg |
| Trebananib 30 mg/kgTrebananib (AMG 386) 30 mg/kg, intravenous infusion. | Drug | Trebananib 30 mg/kg |
Primary outcome
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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.
5 secondary outcomes
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
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
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
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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23124648Doi T, Ohtsu A, Fuse N, Yoshino T, Tahara M, Shibayama K, Takubo T, Weinreich DM. Phase 1 study of trebananib (AMG 386), an angiogenesis targeting angiopoietin-1/2 antagonist, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jan;71(1):227-35. doi: 10.1007/s00280-012-2000-1. Epub 2012 Nov 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trebananib 3 mg/kg, Trebananib 10 mg/kg and Trebananib 30 mg/kg in people with Neoplasms, Advanced Solid, run by Takeda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicity (DLT) (time frame: Day 1 up to Day 28). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02525536, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2015.