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

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)

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.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Other: placebo; Biological: girentuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 864
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Neuquen, Argentina
    • Unidad Oncologica del Neuquen
  • Rosario, Argentina, 2000
    • Centro de Oncologia Rosario
  • Santa Fe, Argentina, S300FFV
    • Clinical Especializada ISIS
  • Buenos Aires
    • Cramer, Buenos Aires, Argentina, 1426
      • Instituto Alexander Fleming
    • Ranelagh, Buenos Aires, Argentina, 1886
      • Hospital Zonal General de Agudos
  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, 1424
      • Complejo Medico de la Policia Federal Argentina
• Brazil
  • Bahia, Brazil, 40170-070
    • Nucleo de Oncologia da Bahia
  • Rio de Janeiro, Brazil, 20230-130
    • Instituto Nacional de Câncer
  • Sao Paulo, Brazil, 01308-050
    • Hospital Sirio-Libanes
  • Sao Paulo, Brazil, 04023-900
    • Universidade Federal de São Paulo
  • Minas Gerais
    • Belo-Horizonte, Minas Gerais, Brazil, 30240-060
      • Biocancer Centro de Pesq e Trat de Cancer SA
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3N1
      • G. Steinhoff Clinical Research
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • McMaster Institute of Urology at St. Joseph Healthcare
    • Oakville, Ontario, Canada, L6H 3PI
      • Male Health Centre - Oakville
    • Oakville, Ontario, Canada, L6J 3J3
      • CMX Research, Incorporated
    • Toronto, Ontario, Canada, M6A 3B5
      • Male Health Centre - North York
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Helen F. Graham Cancer Center at Christiana Hospital
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Atlantic Urological Associates - Daytona Beach
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Tallahassee, Florida, United States, 32308
      • Southeastern Research Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates - Walton Way
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814-2668
      • North Idaho Urology - Coeur d'Alene
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Northeast Indiana Urology, PC
  • Iowa
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Hematology and Oncology Specialists, LLC - Metairie
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Maryland
    • Greenbelt, Maryland, United States, 20770
      • Werner-Francis Urology Associates, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center - Burlington
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute
  • New York
    • Albany, New York, United States, 12209
      • Community Care Physicians, PC at Urological Institute of NENY
    • Bronx, New York, United States, 10466
      • Our Lady of Mercy Medical Center Comprehensive Cancer Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Urology, PC
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists - Greensboro
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Urological Associates of Lancaster, Limited
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Dallas, Texas, United States, 75246
      • Mary Crowley Medical Research Center at Sammons Cancer Center
    • McAllen, Texas, United States, 78503
      • Urology Associates of South Texas, PA
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio, PA - Fredericksburg
  • Vermont
    • Burlington, Vermont, United States, 05405-0110
      • Vermont Cancer Center at University of Vermont
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Heidelberg Pharma AG
• Investigators: Study Director: Pia Kloepfer, MD, Heidelberg Pharma AG

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: July 8, 2004
• First Submitted That Met QC Criteria: July 9, 2004
• First Posted (Estimate): July 12, 2004

Study Record Updates

• Last Update Posted (Actual): November 27, 2018
• Last Update Submitted That Met QC Criteria: October 31, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; stage I renal cell cancer; stage III renal cell cancer; clear cell renal cell carcinoma; stage II renal cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: WX-2003-07-HR; WILEX-WX-2003-07-HR (Other Identifier: WILEX); ARISER (Other Identifier: WILEX); UCLA-0404015-01 (Other Identifier: UCLA); CDR0000372830 (Registry Identifier: PDQ (Physician Data Query)); NCI-2012-00491 (Registry Identifier: CTRP (Clinical Trials Reporting System))