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

Phase 2
18 Years
Not Enrolling
Carcinoma, Renal Cell

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Trial Information

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

Angiogenesis, defined as the growth of new blood vessels from pre-existing vessels, is a
requirement for the growth of nearly all tumors. Clear cell renal cell carcinoma (CCRCC) is
a malignancy characterized by abundant vascularization and a high degree of resistance to
chemotherapy which makes antiangiogenic therapy an intriguing concept for treatment. This
concept has been established by the initial successes observed in recent studies of
antiangiogenic therapies for CCRCC. ATN-161 is an attractive candidate for investigation as
a therapeutic agent in CCRCC because it binds to several fully activated integrins, which
are essential downstream components in the angiogenic signaling cascade.

Functional imaging using dceMRI has been demonstrated as an effective way to show effects on
the vasculature across different tumors, including CCRCC. Preclinical experiments have
shown that ATN-161 affects tumor perfusion in tumor bearing mice. Therefore, use of imaging
in this study is expected to be an effective method for evaluating the antiangiogenic
response to ATN-161.

Patients will be administered ATN-161 three times weekly by short (10 minute) IV infusion at
1 of 3 dose levels (20, 100, and 600 mg). Patients will be treated until progression of
disease, unacceptable drug toxicity, or withdrawal of consent occurs.

Functional imaging (dceMRI) will be performed within 1 week prior to first treatment, again
during the second week of treatment, and finally during the fourth week of treatment.

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

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

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

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

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Reduction in tumor blood flow and permeability of vessels


United States: Food and Drug Administration

Study ID:




Start Date:

August 2005

Completion Date:

Related Keywords:

  • Carcinoma, Renal Cell
  • renal
  • cancer
  • advanced
  • unresectable
  • metastatic
  • recurrent
  • anti-angiogenic
  • targeted
  • ATN-161
  • Recurrent renal cell cancer
  • Renal clear cell carcinoma
  • Advanced Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell



University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
The Cleveland Clinic Foundation Cleveland, Ohio  
University of California Irvine, Chao Family Comprehensive Cancer Center Irvine, California  92868
University of California San Francisco Comprehensive Cancer Center San Francisco, California  94115