A Phase II Study to Treat Subjects With Advanced Renal Cell Carcinoma

A Global, Multicenter, Open-label, Single Agent, Two-stage Phase 2 Study to Evaluate the Efficacy and Safety of AMG 102 in Subjects With Advanced Renal Cell Carcinoma

The purpose of this study is to evaluate the effectiveness and safety of AMG 102 in patients with Advanced Renal Cancer.

Inclusion Criteria:

• documented histologically confirmed advanced or metastatic renal cell carcinoma with the primary tumor in place or following nephrectomy
• measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (CT or MRI) or ≥ 10 mm by spiral CT scan
• no more than 3 relapses (or prior systemic treatments)
• unable to receive or failed prior therapy with vascular endothelial growth factor (VEGF) binding agents or VEGF receptor tyrosine kinase inhibitors or other multi-kinase inhibitors
• tissue blocks or tissue sections from initial or upon diagnosis of advanced metastatic disease are available for submission to the central laboratory within approximately 4 weeks after enrollment or approval is granted by the sponsor (upon receipt of justification why the sample is not available)
• age ≥ 18 years
• ECOG performance status of 0-2
• hemoglobin concentration ≥ 9 g/dL
• absolute neutrophil count ≥ 1.5 x 10(9th)/L
• corrected serum calcium ≤ 10 mg/dL
• either serum creatinine < 2.0 x upper limit of normal OR creatinine clearance > 40 mL/min
• alanine aminotransferase ≤ 2.5 times upper limit of normal or < 5.0 x ULN if the subject has documented liver metastasis or primary hepatic neoplasm
• serum total bilirubin ≤ 2.5 times upper limit of normal
• before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion Criteria:

• active brain metastases; brain metastases allowed provided they have been treated with surgery and/or radiation therapy and show no evidence of progression on cerebral CT or MRI scan 2 months following surgery and/or radiation therapy

• concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months before enrollment) that could compromise participation in the study

• documented history of human immunodeficiency virus infection

• documented history of viral chronic hepatitis

• received biologic, small molecule, immunotherapy, chemotherapy, radiotherapy or other agents to treat renal cancer within 28 days before enrollment

• treated previously with c-Met or HGF targeted therapy

• concurrent or prior (within 7 days before enrollment) anticoagulation therapy, except:

  • Use of low-dose warfarin (< 2 mg/day) for prophylaxis against central venous catheter thrombosis or
  • Use of low molecular weight heparins (LMWH, e.g., enoxaparin sodium [Lovenox] and unfractionated heparin for prophylaxis against central venous catheter thrombosis is allowed

• concurrent use of hormones or other chemotherapeutic agents except for steroids given for adrenal failure and hormones administered for non-disease-related conditions (eg, insulin for diabetes); except for non-cancer reasons

• concurrent palliative or therapeutic radiation therapy

• currently enrolled in or has not yet completed at least 30 days since ending other investigational device or therapy, or subject is receiving other investigational agent(s)

• active infection requiring treatment within 1 week before enrollment

• undergone major surgery within 4 weeks before enrollment or recovering from prior surgery

• past or current history of another neoplasm, except for curatively treated non-melanoma skin cancer, carcinoma in situ of the cervix and other primary solid cancer with no known active disease present and no curative treatment administered for the last 3 years

• known allergy or sensitivity to any of the excipients in the investigational product to be administered

• pregnant or is breast feeding

• not consenting to use adequate contraceptive precautions during the course of the study and for 6 months after the last administration of investigational product:

  • female subjects who are not post-menopausal (no menstrual period for a minimum of 12 months at study entry) or documented surgically sterile will not be bound to this exclusion

• previously treated with AMG 102

• previously enrolled into this study

• will not be available for follow-up assessments

• has other disorders that compromises the ability of the subject to give written informed consent and/or comply with study procedures

• unable to begin protocol specified treatment within 3 days after enrollment