Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
Status and phase
Conditions
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Study type
Funder types
Identifiers
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About
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.
Full 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.
Enrollment
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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Documented histologically confirmed metastatic renal cell carcinoma
- Clear cell histology
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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
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Must have at least one measurable lesion
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If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
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Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)
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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
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No CNS metastases
PATIENT CHARACTERISTICS:
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ECOG performance status < 2
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Life expectancy of at least 4 months
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Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
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Total bilirubin normal
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Platelets > 100,000/mm³
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WBC > 3,500/mm³
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No evidence of congestive heart failure
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No symptoms of coronary artery disease
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No serious cardiac arrhythmias
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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)
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Adequate pulmonary reserve
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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
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Women who are pregnant or lactating are not eligible
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Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
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Negative pregnancy test
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No known HIV-positive patients
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No evidence of active infection requiring antibiotic therapy
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Must not have a contraindication to treatment with pressor agents
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Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
20 participants in 3 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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