Monoclonal Antibody Therapy (Rencarex®) in Treating Patients Who Have Undergone Surgery for Non-metastatic Kidney Cancer

OBJECTIVES:

Primary

- Evaluate the disease-free and overall survival of patients with primary clear cell renal
cell carcinoma at high risk for recurrence treated with chimeric monoclonal antibody
cG250 (WX-G250) vs placebo in an adjuvant setting.

Secondary

- Evaluate the safety of these drugs in these patients.

- Assess the quality of life of patients treated with this drug.

- Perform pharmacokinetic analysis of WX-G250.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to risk criteria and participating centers (US vs Non-US). Patients
are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive monoclonal chimeric antibody cG250 (WX-G250) IV over 15 minutes
once weekly for 24 weeks.

- Arm II: Patients receive placebo IV over 15 minutes once weekly for 24 weeks. In both
arms, treatment continues in the absence of disease progression or unacceptable
toxicity.

Blood samples are collected for pharmacokinetic analysis.

Quality of life is assessed at baseline, at weeks 12 and 24 during treatment, and then at 6
months after completion of study treatment.

Patients are followed every 3 months during years 1 and 2, every 6 months during years 3 and
4, and then annually during year 5 and thereafter.

PROJECTED ACCRUAL: A total of 864 patients out of the expected 856 (428 per treatment arm)
were accrued for this trial.

DISEASE CHARACTERISTICS:

- Histologically confirmed primary clear cell renal cell carcinoma

- Meets 1 of the following high risk criteria:

- T3a, N0/NX, M0 OR T3b, N0/NX, M0 OR T3c, N0/NX, M0 OR T4, N0/NX, M0

- Any T stage and N + disease and M0

- T1b, N0/NX, M0 OR T2, N0/NX, M0, each with grade ≥ 3 (Fuhrman or any other
nuclear grading system with at least 3 grades)

- Prior nephrectomy (total or partial) of primary renal cell carcinoma with documented
clear cell histology within the past 12 weeks

- No evidence of macroscopic or microscopic residual disease

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Platelet count > 100,000/mm^3

- WBC > 3,000/mm^3

- Hemoglobin > 10 g/dL

Hepatic

- AST and ALT < 3 times upper limit of normal (ULN)

- Bilirubin < 1.5 times ULN

- Hepatitis B surface antigen (HbsAg) negative

- Hepatitis C antibody negative

Renal

- Creatinine < 2.0 times ULN

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV I and II negative

- No concurrent unrelated illness which can significantly jeopardize patients' clinical
status

- No active infection

- No inflammation

- No medical condition or laboratory abnormalities that would preclude study
participation

- No other malignancies within the past 5 years except surgically cured nonmelanoma skin
cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 5 years since prior immunotherapy

- No prior murine or chimeric antibody therapy

Chemotherapy

- More than 5 years since prior chemotherapy

Endocrine therapy

- No concurrent corticosteroids above Cushing dose for another disease

- Physiologic corticosteroid replacement therapy allowed at discretion of the
primary investigator

Radiotherapy

- More than 5 years since prior radiotherapy

Surgery

- See Disease Characteristics

- No prior organ transplantation

Other

- No concurrent immunosuppressive agents (e.g., cyclosporine or tacrolimus)