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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00126490
First received: August 2, 2005
Last updated: April 22, 2014
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: bevacizumab
Biological: aldesleukin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Trial of Sequential Bevacizumab Then Subcutaneous Interleukin-2 in Metastatic Renal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Evaluable Participants With Complete Response (CR) and Partial Response (PR) at One Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Major response according to Response Evaluation Criteria In Solid Tumors (RECIST). CR: Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures:
  • Number of Evaluable Participants With Overall Survival (OS) at 2 Years [ Time Frame: 2 years from start of treatment ] [ Designated as safety issue: No ]
    Overall Survival tabulation at 2 years from start of treatment.

  • Number of Evaluable Participants With Progression Free Survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Progression Free Survival tabulation at 1 year and at 2 years. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  • Pearson Correlation Coefficients of Dendritic Cell (DC):Immature Cell (ImC) Ratio With DC Function [ Time Frame: At baseline, at days 4-5, 9-10 (of course 1), and at the end of treatment ] [ Designated as safety issue: No ]
    Dendritic cell (DC) phenotype or functionality. Pearson correlation coefficients of DC:ImC ratio with DC function were to be computed and tested for departure from zero. Those with major responses were to be compared to those without major responses with respect to baseline DC:ImC ratio, baseline DC functional assay, post-treatment DC:ImC ratio and post-treatment DC functional assay using pooled t tests.

  • Number of Participants With Possibly Related Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Number of Participants with Serious Adverse Events (SAEs) Possibly Related to Study Treatment. Toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0


Enrollment: 19
Study Start Date: March 2005
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bevacizumab, aldesleukin)
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Biological: aldesleukin
Given subcutaneously
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the frequency of major response in patients with metastatic renal cell cancer treated with bevacizumab and interleukin-2.

SECONDARY OBJECTIVES I. Compare the median progression-free survival and median overall survival of patients treated with this regimen with risk-stratified historical controls from published risk models.

OUTLINE:

Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 3 months for at least 2 years.

PROJECTED ACCRUAL: Approximately 10-38 patients will be accrued for this study within 21 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed renal cell cancer

    • Metastatic disease
    • More than 75% clear cell histology
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • No prior refractory disease, defined as clinical or radiologic progression, during or within 3 months after completion of prior interleukin-2 (IL-2)
  • Nominally "good" or "intermediate" risk disease, meeting ≥ 4 out of 5 of the following criteria:

    • Hemoglobin > 10 g/dL (except for patients with hereditary hemoglobinopathy)
    • ECOG performance status 0-1 (required)
    • Calcium normal (corrected)

      • Patients with hypercalcemia due to malignancy allowed provided it has been controlled for > 1 month
    • Primary tumor treated or resected by complete nephrectomy, partial nephrectomy, radiofrequency ablation, or other local ablation
    • Lactic dehydrogenase < 1.5 times upper limit of normal (ULN)
  • No history of or current brain or CNS metastasis by CT scan or MRI within the past 30 days
  • Performance status - ECOG 0-1
  • More than 4 months
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • No history of bleeding diathesis
  • PTT < 1.5 times ULN
  • INR < 1.5
  • Bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 2.5 times ULN
  • No chronic hepatitis B or C
  • Creatinine ≤ 2.0 mg/dL
  • No proteinuria* by dipstick urinalysis
  • Urine protein ≤ 1,000 mg by 24-hour urine collection
  • No symptomatic congestive heart failure
  • No uncontrolled hypertension, defined as systolic blood pressure (BP) > 160 mm Hg and diastolic BP > 90 mm Hg
  • No cardiac arrhythmia
  • No peripheral vascular disease ≥ grade 2
  • No clinically significant peripheral artery disease
  • None of the following arterial thromboembolic events within the past 6 months:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina pectoris
    • Myocardial infarction
  • Not pregnant
  • No nursing during and for 3 months after completion of study treatment
  • Negative pregnancy test
  • Fertile patients must use effective contraception before, during, and for 3 months after completion of study treatment
  • No active infection requiring parenteral antibiotics
  • No known HIV positivity
  • No history of allergic reaction to antibody drugs or IL-2
  • No psychiatric illness or social situation that would preclude study compliance
  • No non-healing wound or fracture
  • No insulin-dependent diabetes
  • No other uncontrolled illness
  • No other malignancy requiring active treatment within the past 2 years except nonmelanoma skin cancer
  • No prior bevacizumab
  • At least 6 months since prior immunotherapy containing IL-2
  • At least 2 months since prior investigational antibodies
  • More than 4 weeks since prior conventional cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No concurrent corticosteroids except replacement corticosteroids for adrenal insufficiency OR inhaled steroids for chronic obstructive pulmonary disease, asthma, or allergic rhinitis
  • More than 3 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to the only site of measurable disease unless there has been subsequent disease progression
  • More than 4 weeks since prior major surgery
  • At least 24 hours since prior minor surgical procedure, placement of vascular access device, or fine needle aspiration
  • At least 30 days since prior and no other concurrent investigational agents
  • More than 10 days since prior anticoagulants

    • Low-dose anticoagulants for maintenance of vascular access device patency allowed
  • No concurrent therapeutic warfarin, including warfarin for treatment of deep vein thrombosis or pulmonary embolism
  • No other concurrent anticancer therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126490

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
Investigators
Principal Investigator: Mayer Fishman H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00126490     History of Changes
Other Study ID Numbers: NCI-2012-02663, NCI-2012-02663, CDR0000434852, MCC-IRB-102782, NCI-6438, MCC 13921, 6438, P30CA076292
Study First Received: August 2, 2005
Results First Received: May 29, 2013
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Aldesleukin
Interleukin-2
Antibodies
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014