A Dose-Ranging, Phase II, Open Label Study of ATN 161 in Advanced Renal Cell Cancer

Inclusion Criteria:

1. Patients must have unresectable and/or metastatic kidney cancer with a component of
clear cell adenocarcinoma that is histologically confirmed. A pathologist at the
investigator's institution must have reviewed the material sent by outside
institutions and confirm the diagnosis.

2. Patients must have been previously treated with at least one FDA-approved therapy or
commonly used treatment (such as interferon or low dose interleukin-2) for advanced
kidney cancer. Any number of other prior treatments, approved or investigational, is
acceptable.

3. 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) as
>20 mm with conventional techniques or as 2 times the measurable slice width with
spiral CT scan. See RECIST Appendix B for the evaluation of measurable disease.

4. Patients must have at least one lesion amenable to dceMRI as per lesion guidelines
(see Section 8.1.1).

5. Age ≥18 years.

6. ECOG performance status of 0 or 1 (see Appendix A).

7. Patients must have recovered from the reversible effects of prior treatment (with the
exception of alopecia) by returning to normal or mild severity (Grade 1) or their
pre-treatment baseline.

8. Life expectancy of greater than three months.

9. Patients must have adequate organ and marrow function as defined below:

- absolute neutrophil count ≥1,500 cells/mm3

- platelets ≥100,000 cells/mm3

- total bilirubin ≤1.5 mg/dL

- AST (SGOT) and ALT (SGPT) ≤1.5 x institutional upper limit of normal (ULN) (≤2.5
x ULN for patients with liver metastases)

- alkaline phosphatase ≤5.0 x ULN

- serum creatinine ≤1.5 x ULN

- serum calcium ≤1 x ULN (the patient may be on treatment for hypercalcemia)

10. The effects of ATN 161 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason and because antiangiogenic agents are known to be
teratogenic, women of child-bearing potential and men with partners of child-bearing
potential must agree to use adequate contraception (hormonal and/or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation through the follow up visit 28 days after the last dose of ATN 161.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately. Similarly, if the
partner of a male patient should become pregnant while he is participating in this
study, he should inform his treating physician immediately.

11. Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

1. Patients who have not recovered from reversible adverse events due to
previously-administered agents.

2. Patients may not be receiving any agents, approved or investigational, for the
treatment of CCRCC, and may not be receiving any investigational agents for other
conditions.

3. Patients with documented brain metastases are excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events. Institutional practices should be followed to establish the absence of brain
metastases.

4. 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.

5. Pregnant women are excluded from this study because ATN 161 is an antiangiogenic
agent 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 ATN 161, breastfeeding should be discontinued if the
mother is treated with ATN 161.

6. Patients known to be human immunodeficiency virus (HIV)-positive are excluded.

7. Patients who cannot undergo dceMRI analysis for any reason.

8. Patients who do not have adequate wound healing based on clinical judgment following
a major surgical intervention.