- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
-
-
Connecticut
-
New Haven, Connecticut, États-Unis, 06520-8032
- Yale University
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
|
Étant donné SC
Autres noms:
Given SC
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma
Délai: Continuously throughout study
|
Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
|
Continuously throughout study
|
|
Maximum tolerated dose of recombinant interferon alfa-2b when administered in combination with 5-azacitidine
Délai: Course 1 (4 weeks)
|
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.
|
Course 1 (4 weeks)
|
|
Correlation of promoter methylation with the level of expression of the genes
Délai: Day 5 or 8 and 24 or 26 of course 1
|
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.
|
Day 5 or 8 and 24 or 26 of course 1
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Response rate of giving recombinant interferon alfa-2b when administered in combination with 5-azacitidine in patients with metastatic melanoma and renal cell carcinoma
Délai: Every 8 weeks
|
Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
|
Every 8 weeks
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Mario Sznol, Yale University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs par type histologique
- Tumeurs
- Tumeurs urologiques
- Tumeurs urogénitales
- Tumeurs par site
- Maladies rénales
- Maladies urologiques
- Adénocarcinome
- Carcinome
- Tumeurs, glandulaires et épithéliales
- Attributs de la maladie
- Tumeurs neuroectodermiques
- Tumeurs, cellules germinales et embryonnaires
- Tumeurs, tissu nerveux
- Tumeurs rénales
- Tumeurs neuroendocrines
- Nevi et mélanomes
- Carcinome à cellules rénales
- Récurrence
- Mélanome
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Facteurs immunologiques
- Agents protecteurs
- Agents de radioprotection
- Interférons
- Interféron-alpha
- Interféron alpha-2
- Azacitidine
- Amifostine
Autres numéros d'identification d'étude
- NCI-2009-00152
- YALE HIC#27409
- YALE-HIC-27409
- NCI-7317
- CDR0000441640
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .