Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer

OBJECTIVES:

- Determine the response in patients with metastatic renal cell carcinoma treated with
tretinoin liposome and interferon alfa-2b.

- Determine the toxicity of this regimen in these patients.

- Study retinoic acid receptor expression on tissue obtained from selected patients who
have tumor biopsies.

OUTLINE: This is a dose-escalation study of tretinoin liposome with concurrent individual
dose escalation of interferon alfa-2b. (Phase I closed to accrual as of 9/24/03.)

Patients receive tretinoin liposome IV over 30 minutes once weekly and interferon alfa-2b
subcutaneously on five consecutive days (M-F) for 8 weeks. Courses repeat every 8 weeks in
the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tretinoin liposome until the maximum
tolerated dose (MTD) has been determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined
additional patients are accrued and treated at that dose. (Phase I closed to accrual as of
9/24/03.)

During the first 3 weeks of the study, patients receive interferon alfa-2b at weekly dose
escalations. After week 3, patients continue at the highest acceptable dose level of
interferon alfa-2b for the remainder of the study. (Phase I closed to accrual as of 9/24/03.)

Patients are followed at 30 days after the last treatment.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued into the phase I portion of this
study (Phase I closed to accrual as of 9/24/03). A total of 14-25 patients will be accrued
into the phase II portion of this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic renal cell carcinoma

- Bidimensionally measurable disease

- No active brain metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- More than 3 months

Hematopoietic:

- WBC at least 3,000/mm^3

- Platelet count at least 100,000/mm^3

- No coagulation disorders

Hepatic:

- Bilirubin less than 1.5 mg/dL

- SGOT and SGPT less than 112.5 IU/L each or less than 2.5 times upper limit of normal

- No clinically significant hepatic disease, including autoimmune hepatitis

Renal:

- Creatinine less than 2 mg/dL OR

- Creatinine clearance greater than 50 mL/min

- No clinically significant renal disease

Cardiovascular:

- No clinically significant cardiac disease

- No thrombophlebitis

Pulmonary:

- No severe debilitating pulmonary disease

- No pulmonary embolism

Other:

- No history of diabetes mellitus prone to ketoacidosis

- No known hypersensitivity to retinoids or retinoic acid derivatives or to interferon
or any component of the injection for this study

- No thyroid abnormalities that hinder maintaining thyroid function at the normal range

- No severe infection

- No severe malnutrition

- No clinically significant retinal abnormalities

- No pre-existing psychiatric condition, especially depression or a history of severe
psychiatric disorder

- No other concurrent malignancy except nonmelanoma skin cancer or curatively treated
carcinoma in situ of the cervix

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 effective methods of contraception during and for 1 month
after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No more than 1 prior biological response modifier therapy or immunotherapy

Chemotherapy:

- No more than 1 prior chemotherapy regimen

Endocrine therapy:

- No concurrent steroids

Radiotherapy:

- At least 4 weeks since prior radiotherapy

Surgery:

- At least 4 weeks since prior major surgery

Other:

- No prior retinoid therapy