Bevacizumab and Interleukin-2 in Treating Patients With Metastatic Kidney Cancer

January 9, 2014 updated by: Jonsson Comprehensive Cancer Center

A Phase II Study of Bevacizumab and Aldesleukin in Patients With Metastatic Renal Cell Carcinoma (RCC): A Cytokine Working Group (CWG) Study

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Interleukin-2 may stimulate the white blood cells to kill tumor cells. Giving bevacizumab together with interleukin-2 may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with interleukin-2 works in treating patients with metastatic kidney cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Estimate the response, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma (RCC) treated with bevacizumab and high-dose interleukin-2 (IL-2).

Secondary

  • Compare the response and survival of patients with metastatic RCC treated with bevacizumab and high-dose IL-2 with the historical data of patients treated with high-dose IL-2 alone.
  • Compare the toxicity of bevacizumab and high-dose IL-2 in patients with metastatic RCC with the historical data of patients treated with high-dose IL-2 alone, in terms of number of doses of IL-2 administered during the first course of therapy, toxicity after the scheduled ninth dose of IL-2, and frequency of grade III and IV or unexpected or rare toxicities.
  • Compare the time to disease progression in patients with metastatic RCC treated with bevacizumab and high-dose IL-2 with the historical data of patients treated with high-dose IL-2 alone.
  • Evaluate the pharmacokinetics and pharmacodynamics of bevacizumab and high-dose IL-2 during course 1.
  • Correlate serum vascular endothelial growth factor (VEGF) levels, DC function, TCR zeta chain expression, and arginase or arginine levels with toxicity, response, and survival of patients treated with this regimen.
  • Evaluate the utility of known prognostic criteria for RCC patients on clinical outcome.

OUTLINE: This is a multicenter study. Patients are stratified according to prognosis (good vs intermediate vs poor).

Patients receive bevacizumab IV over 30-90 minutes on days -13, 1, 15, 29, 43, 57, and 71 during course 1 and on days 1, 15, 29, 43, 57, and 71 during courses 2 and 3. Patients also receive high-dose interleukin-2 every 8 hours on days 1-5 and 15-19. Treatment repeats every 84 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1781
        • Recruiting
        • Jonsson Comprehensive Cancer Center at UCLA
        • Contact:
          • Clinical Trials Office - Jonsson Comprehensive Cancer Center a
          • Phone Number: 888-798-0719
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Cardinal Bernardin Cancer Center at Loyola University Medical Center
        • Contact:
          • Clinical Trials Office - Cardinal Bernardin Cancer Center
          • Phone Number: 708-226-4357
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Recruiting
        • Indiana University Melvin and Bren Simon Cancer Center
        • Contact:
          • Clinical Trials Office - Indiana University Cancer Center
          • Phone Number: 317-274-2552
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Recruiting
        • Barbara Ann Karmanos Cancer Institute
        • Contact:
          • Clinical Trials Office - Barbara Ann Karmanos Cancer Institute
          • Phone Number: 313-576-9363
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756-0002
        • Recruiting
        • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
        • Contact:
    • New York
      • Bronx, New York, United States, 10466
        • Recruiting
        • Our Lady of Mercy Medical Center Comprehensive Cancer Center
        • Contact:
          • Janice P. Dutcher, MD
          • Phone Number: 718-304-7200
    • Oregon
      • Portland, Oregon, United States, 97213-2967
        • Recruiting
        • Providence Cancer Center at Providence Portland Medical Center
        • Contact:
          • Clinical Trials Office - Providence Cancer Center at Providenc
          • Phone Number: 503-215-6412
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Cancer Centers
        • Contact:
          • Clinical Trials Office - UPMC Cancer Centers
          • Phone Number: 412-647-8073
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Recruiting
        • Vanderbilt-Ingram Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic renal cell carcinoma (RCC) with predominantly clear cell histology
  • Measurable disease
  • No history of tumor-related hemorrhage
  • No history of CNS or brain metastases

PATIENT CHARACTERISTICS:

  • Karnofsky performance status ≥ 80%
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL (transfusion or recombinant erythropoietin growth factors allowed)
  • AST ≤ 2 times upper limit of normal (ULN) (5 times ULN if due to liver metastases)
  • Serum total bilirubin ≤ 2 times ULN (except for patients with Gilbert's disease)
  • Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min

  • FEV_1 ≥ 2.0 L or ≥ 75% of predicted

    • Pulmonary function testing required for patients over age 50 or with significant pulmonary or smoking history
  • No history of cerebrovascular accident or transient ischemic attacks

  • No evidence of any of the following cardiac conditions*:

    • Congestive heart failure
    • Symptoms of coronary artery disease
    • Myocardial infarction < 6 months prior to study entry
    • Serious cardiac arrhythmias
    • Unstable angina NOTE: *Patients > 40 years old or who have had a previous myocardial infarction > 6 months prior to study entry are required to have a negative or low probability cardiac stress test for cardiac ischemia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

  • No other malignancy within the past 5 years except nonmelanoma skin cancer or noninvasive cancer, such as cervical carcinoma in situ, superficial bladder cancer without local recurrence, or breast cancer in situ

    • Patients with a history of another invasive malignancy must be in complete remission for ≥ 5 years
  • No positive serology for HIV, hepatitis B, or hepatitis C
  • No significant co-morbid illness, such as uncontrolled diabetes or active infection, that would preclude study treatment

  • No history of inflammatory bowel disease or other serious autoimmune disease

    • Thyroiditis or rheumatoid arthritis allowed
  • No uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg)
  • Proteinuria ≤ 3+ by dipstick OR proteinuria < 2 gm by 24-hour urine collection
  • Urine protein:creatinine ration < 1.0
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry
  • No significant traumatic injury within the past 28 days
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No active bleeding
  • No history of other serious hemorrhage, bleeding diathesis, or underlying coagulopathy
  • No history of deep venous thrombosis, clinically significant peripheral vascular disease, or other thrombotic event

PRIOR CONCURRENT THERAPY:

  • No organ allografts
  • At least 4 weeks since prior radiotherapy or surgery and recovered
  • No prior systemic therapy for metastatic RCC
  • No prior bevacizumab or interleukin-2
  • At least 2 weeks since prior steroids
  • No major surgery or open biopsy within the past 28 days
  • No minor surgical procedures, fine needle aspirations, or core biopsies within the past 7 days, except central venous catheter placement
  • No concurrent major surgery
  • No concurrent corticosteroids or other immunosuppressants

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free and overall survival
Response

Secondary Outcome Measures

Outcome Measure
Toxicity
Time to disease progression
Pharmacokinetics and pharmacodynamics
Comparison of response and survival with historical data
Correlation of serum VEGF levels, DC function, TCR zeta chain expression, and arginase or arginine levels with toxicity, response, and survival
Utility of known prognostic criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jonsson Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Study Registration Dates

First Submitted

March 10, 2006

First Submitted That Met QC Criteria

March 10, 2006

First Posted (Estimate)

March 13, 2006

Study Record Updates

Last Update Posted (Estimate)

January 10, 2014

Last Update Submitted That Met QC Criteria

January 9, 2014

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000460074
  • UCLA-050658-01
  • DMS-W0454

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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