Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer
Condition: Advanced Renal Cell Carcinoma; Advanced Sarcomatoid Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Bevacizumab; Pazopanib Hydrochloride; Sorafenib Tosylate; Sunitinib Malate; Trebananib
Intervention description: Given IV; Given PO; Given PO; Given PO; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Sunitinib; Trebananib; Sorafenib; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well trebananib with or without bevacizumab,
      pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate works in treating patients
      with kidney cancer that has spread to other places in the body and usually cannot be cured or
      controlled with treatment (advanced). Trebananib may stop the growth of tumor cells by
      blocking blood flow to the tumor. Immunotherapy with monoclonal, such as bevacizumab, may
      help the body's immune system attack the cancer, and may interfere with the ability of tumor
      cells to grow and spread. Pazopanib hydrochloride, sorafenib tosylate, and sunitinib malate
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or
      by blocking blood flow to the tumor. It is not yet known whether giving trebananib with or
      without bevacizumab, pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate is more
      effective in treating kidney cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed renal cell carcinoma
             except medullary or collecting duct subtypes; sarcomatoid differentiation will be
             allowed

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
             resonance imaging (MRI), or calipers by clinical exam

          -  Patients must have documented radiologic or clinical progressive disease following at
             least one prior anti-VEGF regimen administered either as a single agent or in
             combination with other agents for at least 8 weeks; the prior anti-VEGF treatment
             regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered
             not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks
             after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent
             therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if
             progression on that treatment is observed within 12 weeks of the prior anti-VEGF
             therapy

          -  Any number of prior regimens is allowed; prior investigational therapy is allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

          -  Life expectancy of greater than 3 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< institutional upper limits of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =<
             upper limit of normal (ULN) per institutional laboratory range

          -  International normalized ratio (INR) =< 1.5

          -  Creatinine within normal institutional limits OR creatinine clearance > 40 mL/min per
             24 hour (h) urine collection or calculated according to the Cockcroft-Gault formula

          -  Urinary protein =< 100 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative
             protein is < 1000 mg in a 24 h urine sample

          -  Generally well-controlled blood pressure with systolic blood pressure =< 140 mmHg AND
             diastolic blood pressure =< 90 mmHg prior to enrollment; the use of anti-hypertensive
             medications to control hypertension is permitted

          -  Patients must have a tumor site amenable to biopsy as determined by the treating
             investigator; any questions regarding suitability of a site for biopsy will be
             adjudicated by the principal investigator

          -  Patients must be willing to consent to tumor biopsy for research purposes

          -  Patients should have archival tumor tissue (either unstained slides or tumor blocks)
             available for retrieval

          -  The effects of AMG 386 are known to be detrimental to fetal development; for this
             reason and because inhibitors of angiogenesis as well as other therapeutic agents used
             in this trial are known to be teratogenic, women of child-bearing potential and men
             must agree to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry, for the duration of study participation, and 6
             months after completion of AMG 386; should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately; men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 6 months after completion of AMG 386 and bevacizumab, pazopanib,
             sunitinib, or sorafenib administration

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib;
             Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib
             during prior therapy MAY be eligible if they tolerated the agent after dose level
             reduction (to a minimum of dose level -2 as defined in this protocol)

          -  Central nervous system metastases unless: (1) metastases have been treated and have
             remained controlled for at least two weeks following treatment, AND (2) patient has no
             residual neurological dysfunction off corticosteroids for at least one week; a CT or
             MRI to evaluate for central nervous system (CNS) disease is required for symptomatic
             patients only

          -  History of venous or arterial thromboembolism within 12 months prior to
             enrollment/randomization

          -  History of clinically significant bleeding within 6 months of enrollment/randomization

          -  Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria
             in Adverse Events (CTCAE) version 3.0 or 4.0 >= grade 2 in severity except alopecia

          -  Currently or previously treated with AMG 386, or other molecules that inhibit the
             angiopoietins or Tie2 receptor

          -  Clinically significant cardiovascular disease within 12 months prior to
             enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or
             greater peripheral vascular disease, cerebrovascular accident, transient ischemic
             attack, congestive heart failure, or arrhythmias not controlled by outpatient
             medication or placement of percutaneous transluminal coronary angioplasty/stent

          -  Major surgery within 28 days prior to enrollment or still recovering from prior
             surgery

          -  Minor surgical procedures except placement of tunneled central venous access device
             within 3 days prior to enrollment

          -  Non-healing wound, ulcer (including gastrointestinal), or fracture

          -  Subject not consenting to the use of highly effective contraceptive precautions (e.g.,
             double barrier method [i.e., condom plus diaphragm]) during the course of the study
             and for 6 months after administration of the last study medication

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AMG 386 or the anti-VEGF agent used in study

          -  History of allergic reactions to bacterially-produced proteins

          -  Patients who have had anti-VEGFR tyrosine kinase inhibitor within 1 week, mTOR
             inhibitor within 1 week or anti-VEGF antibody therapy within 3 weeks prior to entering
             the study; patients who have had other forms of chemotherapy or radiotherapy within 4
             weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those
             who have not recovered from adverse events due to agents administered more than 4
             weeks earlier

          -  Patients who have not yet completed at least 21 days (30 days for prior monoclonal
             antibody therapy) since ending other investigational device or drug trials, or who are
             currently receiving other investigational treatments

          -  Patients receiving any medications or substances that are strong inhibitors or
             inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are
             ineligible; caution is advised for patients requiring weak or moderate CYP450 3A4
             inhibitors or inducers; specifically prohibited medicines include indinavir,
             nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone,
             carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's
             wort, and troglitazone

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study because AMG 386, bevacizumab, pazopanib,
             sorafenib, and sunitinib are inhibitors of angiogenesis with the potential for
             teratogenic or abortifacient effects; because there is an unknown but potential risk
             for adverse events in nursing infants secondary to treatment of the mother with AMG
             386, breastfeeding must be discontinued if the mother is treated with AMG 386

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetic interactions with
             pazopanib, sorafenib, or sunitinib; in addition, these patients are at increased risk
             of lethal infections when treated with marrow-suppressive therapy; appropriate studies
             will be undertaken in patients receiving combination antiretroviral therapy when
             indicated

          -  Inability to take oral medications on a continuous basis; patients who are to take
             pazopanib, sorafenib, or sunitinib and are unable to swallow pills whole are
             ineligible (the pills cannot be crushed or broken)

          -  Any condition which in the investigator's opinion makes the subject unsuitable for
             study participation