Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer
Condition: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Anti-Endoglin Chimeric Monoclonal Antibody TRC105; Bevacizumab; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given IV; Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; 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: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well bevacizumab with or without anti-endoglin
      monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has
      spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab
      and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by
      targeting certain cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed renal cancer; all
             histologic subtypes will be eligible

          -  Patients must have metastatic disease which is measurable, 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) to >= 20 mm in the
             long axis by chest x-ray, >= 10 mm in the long axis by spiral computed tomography
             (CT), magnetic resonance imaging (MRI), calipers, or clinical exam, or >= 15 mm in the
             short axis for lymph nodes

          -  Patients must have received at least 1 prior systemic therapy for renal cancer but no
             more than 4 prior therapies; they must have documented intolerance to or progression
             despite at least 1 systemic therapy; therapy administered in the adjuvant setting
             counts toward the prior systemic therapy total; if adjuvant therapy is the patient's
             only prior therapy the disease must have recurred during treatment or within 3 months
             of discontinuation

          -  Allowable prior therapies include VEGF tyrosine kinase inhibitor (TKIs), mammalian
             target of rapamycin (mTOR) inhibitors, and cytokine therapy (example: interleukin-2
             [IL2])

          -  At least 2 weeks must have elapsed from the last dose of the prior systemic therapy
             for biologics and 4 weeks for chemotherapy (6 weeks for nitrosoureas or mitomycin C);
             also note that at least 3 weeks should have elapsed since prior TKI administration

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Life expectancy of greater than 6 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< institutional upper limits or normal (except for Gilbert's)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal (except subjects with liver metastases,
             who can have AST/ALT =< 5 x ULN)

          -  Creatinine glomerular filtration rate (GFR) (calculated or measured) > 50 mL/min

          -  Hemoglobin >= 9 g/dL

          -  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 and for
             the duration of study participation; 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 TRC105 or bevacizumab administration

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had systemic biologic therapy or radiotherapy within 2 weeks prior
             to entering the study or those who have not recovered from adverse events related to
             their prior therapy

          -  Patients who have previously been treated with bevacizumab

          -  Patients who have previously been treated with TRC105

          -  Patients who are receiving any other investigational agents

          -  Known central nervous system (CNS) disease except for treated brain metastasis;
             treated brain metastases are defined as having no ongoing requirement for steroids and
             no evidence of progression or hemorrhage after treatment for at least 3 months, as
             ascertained by clinical examination and brain imaging (MRI or CT) (stable dose of
             anticonvulsants are allowed); treatment for brain metastases may include whole brain
             radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or
             equivalent) or a combination as deemed appropriate by the treating physician; patients
             with CNS metastases treated by neurosurgical resection or brain biopsy performed
             within 3 months prior to day 1 will be excluded

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to TRC105 or bevacizumab

          -  Patients on full-dose anticoagulation will be excluded; antiplatelet therapy will not
             be exclusionary

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, unhealed wound, gastrointestinal fistula, symptomatic congestive heart
             failure, unstable angina pectoris, myocardial infarction, cerebrovascular accident

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother wishes to participate in the study

          -  Patients with a history of bleeding diathesis or inherited coagulopathy are excluded;
             in addition, those with a history of deep vein thrombosis (DVT) or pulmonary embolus
             within 1 year and still requiring active anticoagulation will be excluded; those with
             a more remote history of DVT or pulmonary embolus may be eligible but the risk of
             recurrent thrombosis should be considered

          -  Patients with history of hereditary hemorrhagic telangiectasis (HHT-1 and HHT-2)

          -  Serious or non-healing wound, ulcer, or bone fracture OR history of abdominal fistula,
             gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

          -  Invasive procedures defined as follows:

               -  Major surgical procedure, open biopsy or significant traumatic injury within 28
                  days prior to day 1 therapy

               -  Anticipation of need for major surgical procedures during the course of the study

               -  Core biopsy within 7 days prior to day 1 therapy

          -  Patients with clinically significant cardiovascular disease are excluded:

               -  Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160
                  mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive
                  medication)

               -  History of cerebrovascular accident (CVA) within 6 months

               -  Myocardial infarction or unstable angina within 6 months

               -  New York Heart Association grade II or greater congestive heart failure

               -  Serious and inadequately controlled cardiac arrhythmia

               -  Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)

               -  Clinically significant peripheral vascular disease

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human antibodies

          -  Patients with psychiatric illness/social situations that would limit compliance with
             study requirements will be excluded