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

• ClinicalTrials.gov Identifier: NCT00087022
• Recruitment Status: Completed
• First Posted: July 12, 2004
• Results First Posted: September 12, 2018
• Last Update Posted: November 27, 2018
• Sponsor: Heidelberg Pharma AG
• Information provided by (Responsible Party): Heidelberg Pharma AG

Tracking Information

• First Submitted Date: July 8, 2004
• First Posted Date: July 12, 2004
• Results First Submitted Date: July 2, 2018
• Results First Posted Date: September 12, 2018
• Last Update Posted Date: November 27, 2018
• Study Start Date: July 2004
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2018)

• Disease-free Survival [ Time Frame: Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years) ]
  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.
• Overall Survival [ Time Frame: 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) ]
  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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: August 9, 2018)

• Quality of Life - Global Health Status [ Time Frame: At 12 months ]
  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.
• Pharmacokinetics of WX-G250 [ Time Frame: Week 8 ]
  Quantitative determination of cG250 (Girentuximab) trough serum profiles at week 8 (steady state concentration).

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Kidney Cancer

Intervention

• Biological: girentuximab
  Given IV
  Other Name: Rencarex®, cG250 and WX-G250
• Other: placebo
  Given IV

Study Arms

• 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.
  Intervention: Biological: girentuximab
• Placebo Comparator: Arm II
  Patients receive placebo IV over 15 minutes once weekly for 24 weeks.
  Intervention: Other: placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 29, 2009): 864
• Original Enrollment: Not Provided
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Canada, United States
• Removed Location Countries: Czech Republic, Finland, France, Germany, Norway, Poland, Russian Federation, Spain, Sweden, Ukraine, United Kingdom

Administrative Information

• NCT Number: NCT00087022
• 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) )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Heidelberg Pharma AG
• Original Responsible Party: Not Provided
• Current Study Sponsor: Heidelberg Pharma AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pia Kloepfer, MD; Heidelberg Pharma AG
• Principal Investigator: Arie Belldegrun, MD, FACS; Jonsson Comprehensive Cancer Center

• PRS Account: Heidelberg Pharma AG
• Verification Date: October 2018