pilot study of denileukin diftitox plus high-dose il-2 for patients with metastatic renal cancer

Conditions: Kidney Cancer

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.

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 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 \ 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

Keywords: recurrent renal cell cancer stage iv renal cell cancer clear cell renal cell carcinoma