Clinical trial NCT00479817 (phase 2, status: completed)
Conditions: ovarian cancer, fallopian tube cancer, primary peritoneal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, C57.00, C57.01, C57.02, K65.1, K66.0, N99.4, N73.6, R88.0, Z49.32, Z49.02
Drugs: amg 386, amg 386, paclitaxel, amg 386 placebo
SMILES: [H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C, [H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        In. Criteria -Subjects must have histologically or cytologically documented epithelial
        ovarian (FIGO Stage II-IV), fallopian tube or primary peritoneal cancer.

        (Subjects with pseudomyxoma or mesothelioma are excluded)

          -  Radiographically documented progression per RECIST criteria with modifications or
             progression of CA-125 as defined by the Rustin during or subsequent to the last
             chemotherapy regimen.

          -  May include measurable or non-measurable disease

          -  All scans and x-rays used to document measurable or non-measurable disease must be
             done within 3 weeks (21 days) of enrollment.

          -  No more than 3 previous regimens of anti-cancer therapy. Subjects must have received
             at least one platinum containing regimen

          -  Female 18 years of age or older at the time the written informed consent is obtained

          -  Subjects of child-bearing potential who have not undergone a bilateral
             salpingo-oophorectomy and are sexually active must use an accepted and effective
             non-hormonal method of contraception (ie, double barrier method (eg, condom plus
             diaphragm)) from signing the informed consent through 6 months after last dose of
             study drug.

        Laboratory

          -  Adequate organ and hematological function as evidenced by the following laboratory
             studies within 2 weeks (14 days) of randomization:

          -  Hematological function, as follows:

        Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L and ≤ 850 x
        109/L Hemoglobin ≥ 9 g/dL PTT or aPTT≤ 1.5 x ULN per institutional laboratory rand and INR
        ≤ 1.5 x 109/L per instiutiona laboratory range

        Renal function, as follows:

        Creatinine ≤ 2.0 mg/dL Calculated creatinine clearance > 40 cc/min according to the
        Cockcroft-Gault formula

        -Hepatic function, as follows: Total bilirubin ≤ 2.0 x ULN SGOT (AST) and SGPT (ALT) ≤ 2.5
        x ULN (≤ 5 x ULN if liver metastases are present) Nutritional

          -  Albumin ≥ 2.8 mg/dL General

          -  GOG Performance Status of 0 or 1

          -  Subject plans to begin protocol directed therapy within 7 days of randomization Ex
             Criteria

          -  Subjects believed to be a higher than average risk for bowel perforation. This
             includes symptoms of partial or complete bowel obstruction, recent (within 6 months)
             history of fistula or bowel perforation, subjects requiring total parenteral nutrition
             and continuous hydration

          -  Known ongoing small bowel dysfunction (ie, persistent nausea, vomiting)

          -  Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all
             radiotherapy-related toxicities

          -  If all sites of disease have been irradiated, documented progression must have
             occurred in at least one site of disease subsequent to the radiation therapy.

          -  Previous abdominal radiotherapy

          -  Has not yet completed a 21 day washout period for any previous anti-cancer systemic
             therapies (60 days for bevacizumab or any molecule of long half-life).

          -  Enrolled in or has not yet completed at least 30 days since ending other
             investigational device or drug study(s), or is receiving other investigational
             agent(s)

          -  Current or prior history of central nervous system metastasis

          -  Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral
             neuropathy ≥grade 2

          -  History of arterial or venous thrombosis within 12 months prior to randomization

          -  Concurrent or prior (within 1 week before study day 1) anticoagulation therapy,
             excluding aspirin and anti platelet agents. The concurrent use of low molecular weight
             heparin or low dose warfarin (ie, ≤ 1 mg daily) for prophylaxis against thrombosis is
             acceptable while on study

          -  History of bleeding diathesis or clinically significant bleeding within 14 days of
             randomization

          -  Major surgical procedure within 4 weeks (28 days) prior to Study Day 1

          -  Minor surgical procedure, or placement of central venous access device, within 7 days
             of Study Day 1

          -  Paracentesis and/or thoracentesis are permitted prior to and while on study at the
             discretion of the investigator as clinically indicated. Investigators should document
             the frequency of paracenteses and/or thoracentesis that occurred prior to the
             enrollment of the subject in this study on the appropriate eCRFs. Investigators should
             also document each paracentesis and/or thoracentesis that occurs while a subject is on
             study on the appropriate eCRFs.

          -  Subjects with a history of prior malignancy, except:

          -  Malignancy treated with curative intent and with no known active disease present for ≥
             3 years before enrollment and felt to be at low risk for recurrence by treating
             physician

          -  Adequately treated non melanomatous skin cancer or lentigo maligna without evidence of
             disease

          -  Adequately treated cervical carcinoma in situ without evidence of disease

          -  Prior myeloablative high dose chemotherapy with allogeneic or autologous stem cell (or
             bone marrow) transplant

          -  Clinically significant cardiac disease within 12 months of study enrollment, including
             myocardial infarction, unstable angina, grade 2 or greater peripheral vascular
             disease, congestive heart failure, or arrhythmias not controlled by outpatient
             medication, percutaneous transluminal coronary angioplasty/stent

          -  Non-healing wound, ulcer or fracture

          -  Ongoing or active infection

          -  Unacceptable hypersensitivity to paclitaxel or drugs containing cremophor

          -  Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis
             B surface antigen

          -  Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1
             or TIE-2 including, but not limited to, AMG 386, XL880, XL820

          -  Prior therapy against vascular endothelial growth factor or the vascular endothelial
             growth factor receptors including, but not limited to, bevacizumab, sunitinib,
             sorafenib, motesanib (AMG 706) or cediranib (AZD-2171), is permitted so long as the
             agent does not have any known activity against angiopoietin 1 or 2, or the receptors
             TIE-1 or TIE-2

          -  Current or within 30 days of randomization treatment with immune modulators such as
             cyclosporine and tacrolimus