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
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: 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 August 21, 2014