Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
- Conditions
- Kidney Cancer
- Interventions
- Biological: aldesleukinBiological: denileukin diftitox
- Registration Number
- NCT00278369
- Lead Sponsor
- Northwestern University
- Brief Summary
RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.
- Detailed Description
OBJECTIVES:
Primary
* Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.
Secondary
* Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.
* Determine the overall response rate (partial and complete) in patients treated with this regimen.
* Determine the time to progression in patients treated with this regimen.
OUTLINE: This is a randomized, pilot study.
The first 3 patients enrolled in the study receive high-dose interleukin-2 (IL-2) IV over 15 minutes, 3 times daily, on days 1-5 and 15-19 and denileukin diftitox IV over 15-60 minutes once daily on days 8-10. If no dose-limiting toxicity occurs after receiving denileukin diftitox, subsequent patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes once daily on days -4 to -2 and high-dose IL-2 IV over 15 minutes, 3 times daily, on days 1-5 and 15-19.
* Arm II: Patients receive high-dose IL-2 as in arm I and denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes at a higher dose once daily on days 8-10.
All patients may receive additional treatment with IL-2 alone in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for at least 4 years.
PROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A aldesleukin 6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course A denileukin diftitox 6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course B aldesleukin 9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course B denileukin diftitox 9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course C aldesleukin 9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course C denileukin diftitox 9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
- Primary Outcome Measures
Name Time Method The primary objective is to assess for toxicity After each cycle of therapy and 30 days after the last treatment. To assess the toxicity
- Secondary Outcome Measures
Name Time Method The secondary objectives are to investigate differences in peak and duration of the expansion of CD4+, CD8+, CD4+CD 25+ and CD56+(dim and bright)CD25+ cells Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks. To investigate differences in peak and duration.
To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels Cohort 1: Denileukin diftitox dose of 6μg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9μg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9μg/kg given days 8 and 9. To investigate the effects of denileukin diftitox
To perform TGF-beta promoter and TGF-beta receptor genotyping prior to the start of treatment to search for variants that may be associated with tumor response to therapy. Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5. To perform TGF-beta promoter and TGF-beta receptor genotyping
Overall response rate and time to progression CT scans and other pertinent studies will be performed at week 10 to assess response. Overall response rate will be assessed.
Trial Locations
- Locations (1)
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States