Clinical trial NCT00087022: Monoclonal Antibody Therapy (Rencarex®) in Treating Patients Who Have Undergone Surgery for Non-metastatic Kidney Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Cancer
Keywords: 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
Lead sponsor: Heidelberg Pharma AG
Sponsor class: INDUSTRY
First posted: 2004-07-12
Enrollment: 864
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Disease-free Survival
timeFrame: Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years)
measure: Overall Survival
timeFrame: 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 outcomes:
measure: Quality of Life - Global Health Status
timeFrame: At 12 months
measure: Pharmacokinetics of WX-G250
timeFrame: Week 8
Other outcomes:
Locations:
city: Anchorage
country: United States
state: Alaska
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Newark
country: United States
facility: Helen F. Graham Cancer Center at Christiana Hospital
state: Delaware
city: Daytona Beach
country: United States
facility: Atlantic Urological Associates - Daytona Beach
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tallahassee
country: United States
facility: Southeastern Research Group
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Augusta
country: United States
facility: Augusta Oncology Associates - Walton Way
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Urology - Coeur d'Alene
state: Idaho
city: Fort Wayne
country: United States
facility: Northeast Indiana Urology, PC
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Metairie
country: United States
facility: Hematology and Oncology Specialists, LLC - Metairie
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Shreveport
country: United States
facility: Feist-Weiller Cancer Center at Louisiana State University Health Sciences
state: Louisiana
city: Greenbelt
country: United States
facility: Werner-Francis Urology Associates, LLC
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic Medical Center - Burlington
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Albany
country: United States
facility: Community Care Physicians, PC at Urological Institute of NENY
state: New York
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Urology, PC
state: New York
city: Greensboro
country: United States
facility: Alliance Urology Specialists - Greensboro
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Lancaster
country: United States
facility: Urological Associates of Lancaster, Limited
state: Pennsylvania
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center at Sammons Cancer Center
state: Texas
city: McAllen
country: United States
facility: Urology Associates of South Texas, PA
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio, PA - Fredericksburg
state: Texas
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Cramer
country: Argentina
facility: Instituto Alexander Fleming
state: Buenos Aires
city: Ranelagh
country: Argentina
facility: Hospital Zonal General de Agudos
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Complejo Medico de la Policia Federal Argentina
state: Capital Federal
city: Neuquen
country: Argentina
facility: Unidad Oncologica Del Neuquen
city: Rosario
country: Argentina
facility: Centro de Oncologia Rosario
city: Santa Fe
country: Argentina
facility: Clinical Especializada ISIS
city: Belo-Horizonte
country: Brazil
facility: Biocancer Centro de Pesq e Trat de Cancer SA
state: Minas Gerais
city: Bahia
country: Brazil
facility: Nucleo de Oncologia da Bahia
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
city: Sao Paulo
country: Brazil
facility: Hospital Sirio-Libanes
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
city: Victoria
country: Canada
facility: G. Steinhoff Clinical Research
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster Institute of Urology at St. Joseph Healthcare
state: Ontario
city: Oakville
country: Canada
facility: Male Health Centre - Oakville
state: Ontario
city: Oakville
country: Canada
facility: CMX Research, Incorporated
state: Ontario
city: Toronto
country: Canada
facility: Male Health Centre - North York
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
Study officials:
affiliation: Heidelberg Pharma AG
name: Pia Kloepfer, MD
role: STUDY_DIRECTOR
affiliation: Jonsson Comprehensive Cancer Center
name: Arie Belldegrun, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chamie K, Donin NM, Klopfer P, Bevan P, Fall B, Wilhelm O, Storkel S, Said J, Gambla M, Hawkins RE, Jankilevich G, Kapoor A, Kopyltsov E, Staehler M, Taari K, Wainstein AJA, Pantuck AJ, Belldegrun AS. Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):913-920. doi: 10.1001/jamaoncol.2016.4419.
citation: Donin NM, Pantuck A, Klopfer P, Bevan P, Fall B, Said J, Belldegrun AS, Chamie K. Body Mass Index and Survival in a Prospective Randomized Trial of Localized High-Risk Renal Cell Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016 Sep;25(9):1326-32. doi: 10.1158/1055-9965.EPI-16-0226. Epub 2016 Jul 14.