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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether monoclonal antibody therapy is effective in treating kidney cancer. PURPOSE: This randomized phase III trial is studying monoclonal antibody therapy to see how well it works in treating patients who have undergone surgery for nonmetastatic primary kidney cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
A Randomized, Double Blind Phase III Study To Evaluate Adjuvant cG250 Treatment Versus Placebo In Patients With Clear Cell RCC And High Risk of Recurrence (ARISER)

Conditions
-----------------
Kidney Cancer

Intervention / Treatment
-----------------
* Biological: girentuximab
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive monoclonal chimeric antibody cG250 (synonym names: Rencarex®, girentuximab, and WX-G250) IV over 15 minutes once weekly for 24 weeks. | Biological: girentuximab<br>* Given IV<br>* Other names: Rencarex®, cG250 and WX-G250;|
| Placebo Comparator: Arm II<br>Patients receive placebo IV over 15 minutes once weekly for 24 weeks. | Other: placebo<br>* Given IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival | Disease Free Survival (DFS) calculated from the date of randomization up to and including the date of documented relapse as confirmed by the CT, death or start of new anti-tumor therapy. | Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years) | 
| Overall Survival | Overall Survival (OS) calculated from the date of randomization to the date of death. Patients with no documented death will be censored at the date of their last study evaluation. | After 419 OS events or 60 months after the last patient has been enrolled, whichever is the later (median follow-up of 4.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life - Global Health Status | Quality of life by EORTC Quality of Life Questionnaire-C30 - Global Health Status at 12 months. A high score for the global health status/QoL represents a high QoL with 0 being the minimum and 100 being the maximum. | At 12 months | 
| Pharmacokinetics of WX-G250 | Quantitative determination of cG250 (Girentuximab) trough serum profiles at week 8 (steady state concentration). | Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
clear cell renal cell carcinoma, stage I renal cell cancer, stage II renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer