RATIONALE: RPI.4610 may stop the growth of metastatic kidney cancer by stopping blood flow
to the tumor.
PURPOSE: Phase II trial to study the effectiveness of RPI.4610 in treating patients who have
metastatic kidney cancer.
OBJECTIVES: I. Determine the response rate of patients with metastatic renal cell cancer
treated with RPI.4610. II. Determine the percentage of these patients with stable disease at
16 weeks after starting treatment with this drug. III. Assess the safety and tolerability of
this drug in these patients.
OUTLINE: This is a multicenter study. Patients receive RPI.4610 subcutaneously daily.
Treatment continues for 16 weeks in the absence of disease progression or unacceptable
toxicity. Patients with stable or responding disease may continue treatment after 16 weeks.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed clear cell renal cell cancer Stage IV
Measurable disease Bone metastases may not be only measurable lesions Failed prior
interleukin-2 (IL-2) therapy (with or without interferon) or ineligible or intolerant of
IL-2 Prior nephrectomy (radical, partial, or laparoscopic) at least 4 weeks ago No CNS
metastases on CT scan or MRI of head
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life
expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Platelet count at least
100,000/mm3 Hemoglobin greater than 9.5 g/dL No history of bleeding disorder Hepatic: AST
or ALT no greater than 3 times upper limit of normal (ULN) Bilirubin no greater than 1.5
times ULN (unless history of Gilbert's syndrome) Alkaline phosphatase no greater than 2.5
times ULN PT no greater than 15 sec INR no greater than 1.5 No history of cirrhosis Renal:
Creatinine no greater than 2.0 mg/dL Cardiovascular: No New York Heart Association class
III or IV heart disease No uncontrolled hypertension, defined as newly diagnosed but
untreated or treated but with diastolic blood pressure at least 95 mmHg or systolic blood
pressure at least 160 mmHg Other: HIV negative No systemic infection requiring antibiotics
within the past 28 days No other malignancy within the past 5 years except basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix No alcohol or drug abuse
within the past 2 years No other medical or psychiatric condition that would preclude
study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective
contraception during and for 1 month after study
PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 4 weeks
since prior IL-2 At least 6 months since prior biotherapy for metastases (e.g., vaccines,
matrix metalloproteinase inhibitors, or antibody therapy) No prior antiangiogenic agent,
including thalidomide, or experimental antiangiogenic agents No concurrent immunotherapy
No other concurrent biotherapy Chemotherapy: No prior chemotherapy for metastatic renal
cell cancer No concurrent chemotherapy Endocrine therapy: No concurrent estrogens or other
hormonal therapy including androgens Concurrent replacement doses of steroids allowed
provided stable for the past 28 doses Radiotherapy: At least 8 weeks since prior
radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics At least 4
weeks since prior major surgery Other: At least 4 weeks since prior investigational drugs
No other concurrent investigational drugs No concurrent immunosuppressive medications No
concurrent warfarin, heparin, low molecular weight heparin, or other anticoagulant agents