A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Trebananib (AMG 386 ) in Adult Japanese Participants With Advanced Solid Tumors
Condition: Neoplasms, Advanced Solid
Intervention: Trebananib 3 mg/kg; Trebananib 10 mg/kg; Trebananib 30 mg/kg
Intervention description: Trebananib (AMG 386) 3 mg/kg, intravenous infusion.; Trebananib (AMG 386) 10 mg/kg, intravenous infusion.; Trebananib (AMG 386) 30 mg/kg, intravenous infusion.
Intervention MeSH terms: Trebananib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 20 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Drug Therapy

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.
    

Eligibility criteria:

        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.