- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00217542
Azacitidine and Recombinant Interferon Alfa-2b in Treating Patients With Stage III or Stage IV Melanoma or Stage IV Kidney Cancer That Cannot Be Removed By Surgery
A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
I. Determine the adverse event profile and maximum tolerated dose of interferon alfa-2b when combined with azacitidine in patients with unresectable stage III or IV melanoma or unresectable stage IV renal cell carcinoma.
II. Determine the feasibility of this regimen for future phase II trials.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive azacitidine subcutaneously (SC) once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 2-4 months.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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Connecticut
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New Haven, Connecticut, Forenede Stater, 06520-8032
- Yale University
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
Histologically confirmed diagnosis of 1 of the following:
Melanoma
- Unresectable stage III disease
- Stage IV disease
Renal cell carcinoma
- Unresectable and/or stage IV disease
- Measurable disease
No untreated brain metastases or leptomeningeal disease
- Patients with previously treated brain metastases are eligible provided they have no evidence of progression for ≥ 4 weeks following treatment and do not require steroids
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 3 months
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL (may be transfused to this level)
- PT or PTT < 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/mL
- AST and ALT ≤ 3 times ULN (5 times ULN for patients with liver metastases)
- Albumin ≥ 3.0 g/dL
- Creatinine ≤ 1.7 mg/dL
- Creatinine clearance ≥ 50 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No ventricular cardiac arrhythmia
- No myocardial infarction within the past 3 months
- No dyspnea at rest
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active gastrointestinal bleeding or ulcer disease
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study agents
- At least 2 weeks since prior immunotherapy
- Prior adjuvant interferon alfa for metastatic disease or in the adjuvant setting allowed
- At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin)
- See Disease Characteristics
- At least 2 weeks since prior hormonal therapy
- At least 1 week since prior and no concurrent steroids
- At least 3 weeks since prior radiotherapy
- At least 2 weeks since prior minor surgery
- At least 3 weeks since prior major surgery
- Recovered from all prior therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Treatment (chemotherapy, biological therapy)
Patients receive azacitidine SC once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.
Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
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Givet SC
Andre navne:
Given SC
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma
Tidsramme: Continuously throughout study
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Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
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Continuously throughout study
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Maximum tolerated dose of recombinant interferon alfa-2b when administered in combination with 5-azacitidine
Tidsramme: Course 1 (4 weeks)
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Toxicity will be graded according to the NCI CTCAE version 3.0.
The MTD is the highest dose level in which < 2 patients of 6 develop first cycle DLT.
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Course 1 (4 weeks)
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Correlation of promoter methylation with the level of expression of the genes
Tidsramme: Day 5 or 8 and 24 or 26 of course 1
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Determined by Western blotting, immunohistochemistry, and/or RT-PCR.
We will use Western blot analysis when antibodies are available and semi-quantitative RT-PCR in cases where antibodies are not available.
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Day 5 or 8 and 24 or 26 of course 1
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Response rate of giving recombinant interferon alfa-2b when administered in combination with 5-azacitidine in patients with metastatic melanoma and renal cell carcinoma
Tidsramme: Every 8 weeks
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Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
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Every 8 weeks
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Mario Sznol, Yale University
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Neoplasmer efter histologisk type
- Neoplasmer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Nyresygdomme
- Urologiske sygdomme
- Adenocarcinom
- Karcinom
- Neoplasmer, kirtel og epitel
- Sygdomsegenskaber
- Neuroektodermale tumorer
- Neoplasmer, kimceller og embryonale
- Neoplasmer, nervevæv
- Nyre-neoplasmer
- Neuroendokrine tumorer
- Nevi og melanomer
- Karcinom, nyrecelle
- Tilbagevenden
- Melanom
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Antivirale midler
- Enzymhæmmere
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunologiske faktorer
- Beskyttelsesagenter
- Strålebeskyttende midler
- Interferoner
- Interferon-alfa
- Interferon alfa-2
- Azacitidin
- Amifostin
Andre undersøgelses-id-numre
- NCI-2009-00152
- YALE HIC#27409
- YALE-HIC-27409
- NCI-7317
- CDR0000441640
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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