Clinical trial NCT00508625 (phase 2, status: completed)
Conditions: non-small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: amg 951 (rhapo2l/trail), bevacizumab, carboplatin, paclitaxel
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, N[C@@H](CCCNC(N)=N)C(O)=O, [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
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC). Mixed
             tumors will be categorized by the predominant cell type unless small cell elements are
             present in which case the patient is ineligible. Cytologic or histologic elements can
             be established on metastatic tumor aspirates or biopsy.

          -  Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural
             effusion or Stage IV or recurrent disease. Subjects with unmeasurable but evaluable
             disease can be included in the phase 1b study, but disease must be measurable to be
             included in the phase 2 study

          -  Planning to receive up to 6 cycles of chemotherapy

          -  ECOG performance status of 0 or 1

          -  Life expectancy greater than 3 months

          -  ≥18 years old

          -  Subjects must sign and date a written Independent Ethics Committee (IEC)-approved
             Informed Consent Form

          -  INR ≤ 1.2 and PTT ≤ ULN within 1 week prior to enrollment

        Exclusion Criteria:

        Disease Related

          -  Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ
             cervical cancer), unless have been treated with curative intent with no evidence of
             disease for > 3 years

          -  Untreated or unstable central nervous system (CNS) metastases. Subjects with treated
             and stably controlled CNS metastases are eligible for cohorts A and B of the phase 2
             part of the study if definitive therapy has been administered (surgery and/or
             radiation therapy), there is no planned treatment for brain metastases, and the
             subject is clinically stable and is off corticosteroids or on a stable dose of
             corticosteroids for at least 2 weeks prior to enrollment

          -  Myocardial infarction, or unstable or uncontrolled disease or condition related to or
             impacting cardiac function (e.g., unstable angina, congestive heart failure [New York
             Heart Association > class II]) within 1 year of enrollment

          -  Uncontrolled hypertension defined as: systolic blood pressure > 150 mm Hg OR diastolic
             blood pressure > 100 mm Hg (antihypertensive therapy to achieve these parameters is
             allowable)

          -  History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic
             disorders within 1 year of enrollment

          -  Recent major surgical procedure within 28 days of enrollment

          -  Subjects must not have serious non-healing wound ulcer, or bone fracture within 21
             days prior to enrollment

          -  Persistent history of gross hemoptysis (defined as bright red blood of a ½ teaspoon or
             more) related to subject's NSCLC

          -  Known (documented in medical notes) HIV infection

          -  Active infection on day of enrollment

          -  Known to be hepatitis C positive OR hepatitis B surface antigen positive

          -  Subjects with Gilbert's syndrome

        Laboratory

          -  Absolute neutrophil count (ANC) < 1.5 x 10*9 /L (without granulocyte-colony
             stimulating factor support within 2 weeks of enrollment)

          -  Platelet count < 100 x 10*9 /L (without transfusion within 2 weeks of enrollment)

          -  Hemoglobin < 9 g/dL (subjects may be transfused or receive erythropoietic treatment to
             meet criterion)

          -  Urine protein quantitative value of > 1+ on dipstick or > 30 mg/dL in urinalysis. If
             quantitative protein is < 500 mg in 24-hour urine collection then subject can be
             included

          -  Significant liver dysfunction as defined by aspartate aminotransferase (AST) or
             alanine aminotransferase (ALT) > 2.5 x upper limits of normal (ULN)

          -  Alkaline phosphatase > 2.5 x ULN, or alkaline phosphatase > 5 x ULN in the presence of
             bone or liver metastasis

          -  Total bilirubin > 1.5 x ULN

          -  Calculated creatinine clearance < 50 mL/min.

          -  Hypercalcemia (serum calcium > 12.0 mg/dL or symptomatic)

        Medications

          -  Prior chemotherapy (except for adjuvant chemotherapy, provided the last dose of
             adjuvant therapy was received at least one year prior to enrollment), hormonal
             therapy, radiotherapy (except palliative radiotherapy for bone metastases or radiation
             therapy for CNS metastases) or immunotherapy for treatment of advanced NSCLC

          -  Prior drug treatment or therapy with investigational agents for NSCLC

          -  Therapeutic anticoagulation treatment. Prophylactic anticoagulation of venous access
             devices (eg, with low-dose warfarin [1-2mg/day] or low-dose heparin) is allowed
             providing INR ≤ 1.2 and PTT is ≤ ULN within 1 week prior to enrollment

          -  Chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory
             agents known to inhibit platelet function. Treatment with dipyridamole, ticlopidine,
             clopidogrel and/or cilostazol is also not allowed.

        General Exclusions

          -  Participation in clinical trials or undergoing other investigational procedures within
             30 days before study enrollment

          -  Subject is evidently pregnant (e.g. positive HCG test) or is breast feeding

          -  Woman or man with partner of childbearing potential not consenting to use adequate
             contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus
             condom), or abstinence during the course of the study and for 6 months after the last
             study drug administration for women, and 1 month for men.

          -  Subject has known sensitivity to any of the products to be administered during the
             study.

          -  Subject has any kind of disorder that compromises the ability of the subject to give
             written informed consent and/or comply with study procedures.

          -  Any condition which in the investigator's opinion makes the subject unsuitable for
             study participation

          -  Subjects enrolled and dosed in phase 1b will be excluded from phase 2

        Exclusion criteria for phase 1b and bevacizumab treatment (cohorts C, D and E) in phase 2

          -  Subjects with central nervous system tumor involvement

          -  Subjects with squamous NSCLC