Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Timothy Kuzel, Northwestern University
ClinicalTrials.gov Identifier:
NCT00278369
First received: January 16, 2006
Last updated: May 20, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Biological: aldesleukin
Biological: denileukin diftitox
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • The primary objective is to assess for toxicity [ Time Frame: After each cycle of therapy and 30 days after the last treatment. ] [ Designated as safety issue: Yes ]
    To assess the toxicity


Secondary Outcome Measures:
  • 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 [ Time Frame: Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks. ] [ Designated as safety issue: No ]
    To investigate differences in peak and duration.

  • To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To perform TGF-beta promoter and TGF-beta receptor genotyping

  • Overall response rate and time to progression [ Time Frame: CT scans and other pertinent studies will be performed at week 10 to assess response. ] [ Designated as safety issue: No ]
    Overall response rate will be assessed.


Enrollment: 20
Study Start Date: April 2005
Study Completion Date: September 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
Biological: aldesleukin
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment
Other Names:
  • IL-2
  • Interleukin-2
  • Proleukin
Biological: denileukin diftitox
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Other Names:
  • ONTAK (denileukin diftitox)
  • DAB 389 IL-2
Experimental: B
9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course
Biological: aldesleukin
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment
Other Names:
  • IL-2
  • Interleukin-2
  • Proleukin
Biological: denileukin diftitox
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Other Names:
  • ONTAK (denileukin diftitox)
  • DAB 389 IL-2
Experimental: C
9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
Biological: aldesleukin
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment
Other Names:
  • IL-2
  • Interleukin-2
  • Proleukin
Biological: denileukin diftitox
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Other Names:
  • ONTAK (denileukin diftitox)
  • DAB 389 IL-2

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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Documented histologically confirmed metastatic renal cell carcinoma

    • Clear cell histology
  • Disease must be measurable as defined by lesions that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques or > 10 mm with spiral CT scan

    • Must have at least one measurable lesion
    • If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
    • Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)
    • The following are considered nonmeasurable lesions:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Cystic lesions
      • Abdominal masses not confirmed and followed by imaging techniques
  • No CNS metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status < 2
  • Life expectancy of at least 4 months
  • Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
  • Total bilirubin normal
  • Platelets > 100,000/mm³
  • WBC > 3,500/mm³
  • No evidence of congestive heart failure
  • No symptoms of coronary artery disease
  • No serious cardiac arrhythmias
  • A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms are present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)
  • Adequate pulmonary reserve

    • Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment

      • FEV_1 > 2.0 liters of > 75% predicted for height and age
      • Patients unable to perform PFTs will be excluded
  • Women who are pregnant or lactating are not eligible
  • Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
  • Negative pregnancy test
  • No known HIV-positive patients
  • No evidence of active infection requiring antibiotic therapy
  • Must not have a contraindication to treatment with pressor agents
  • Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study
  • No history of another malignancy within the past 5 years other than basal cell skin cancer

PRIOR CONCURRENT THERAPY:

  • Recovered from all toxic effects of prior therapy
  • Must not currently receive chronic medication for asthma
  • No prior interleukin-2 (IL-2) therapy
  • No prior organ allografts
  • No systemic corticosteroids in the 4 weeks prior to treatment
  • No concurrent systemic steroids
  • No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment
  • No concurrent radiotherapy, chemotherapy, or other immunotherapy
  • No previous investigational agent within 4 weeks prior to the start of study treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00278369

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
Investigators
Study Chair: Timothy M. Kuzel, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Timothy Kuzel, Timothy Kuzel, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00278369     History of Changes
Other Study ID Numbers: NU 04U1, P30CA060553, NU-04U1, STU00006770
Study First Received: January 16, 2006
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
recurrent renal cell cancer
stage IV renal cell cancer
clear cell renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Denileukin diftitox
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014