- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00278369
Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Tidlig fase 1
Kontakter og plasseringer
Studiesteder
-
-
Illinois
-
Chicago, Illinois, Forente stater, 60611-3013
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: A
6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
|
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
Andre navn:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Andre navn:
|
Eksperimentell: B
9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course
|
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
Andre navn:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Andre navn:
|
Eksperimentell: C
9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
|
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
Andre navn:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
The primary objective is to assess for toxicity
Tidsramme: After each cycle of therapy and 30 days after the last treatment.
|
To assess the toxicity
|
After each cycle of therapy and 30 days after the last treatment.
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
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
Tidsramme: 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.
|
Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.
|
To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels
Tidsramme: 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
|
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 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.
Tidsramme: 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
|
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.
|
Overall response rate and time to progression
Tidsramme: CT scans and other pertinent studies will be performed at week 10 to assess response.
|
Overall response rate will be assessed.
|
CT scans and other pertinent studies will be performed at week 10 to assess response.
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Nyresykdommer
- Urologiske sykdommer
- Nyre-neoplasmer
- Fysiologiske effekter av legemidler
- Anti-infeksjonsmidler
- Agenter fra det perifere nervesystemet
- Antivirale midler
- Anti-HIV-midler
- Antiretrovirale midler
- Analgetika
- Sensoriske systemagenter
- Analgetika, ikke-narkotisk
- Antineoplastiske midler
- Aldesleukin
- Interleukin-2
- Denileukin diftitox
Andre studie-ID-numre
- NU 04U1
- P30CA060553 (U.S. NIH-stipend/kontrakt)
- NU-04U1
- STU00006770 (Annen identifikator: Northwestern University IRB)
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