- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00387465
Azacitidine and Entinostat in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer
A Phase I/II Study of Entinostat in Combination With 5-Azacytidine in Patients With Recurrent Advanced Non-Small Cell Lung Cancer
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
PRIMARY OBJECTIVES:
I. To assess safety, characterize toxicities, and determine the maximum tolerated dose of 5-AZA (azacitidine) with a fixed-dose of entinostat in patients with recurrent advanced non-small cell lung cancer (NSCLC). (Phase I) II. To determine the objective response rate of 5-AZA and entinostat in patients with recurrent NSCLC. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the pharmacokinetic profile of 5-AZA and entinostat in patients with recurrent NSCLC.
II. To assess the pharmacodynamic effects of 5-AZA and entinostat on deoxyribonucleic acid (DNA) methylation, histone acetylation, and gene re-expression in patients with recurrent NSCLC through analysis of blood, sputum and tissue biopsies.
III. To explore the effect of 5-AZA and entinostat on progression-free and overall survival in patients with recurrent advanced non-small cell lung cancer.
IV. To explore the differing response rates and progression-free survivals of two schedules of 5-AZA and entinostat in patients with recurrent advanced non-small cell lung cancer.
OUTLINE: This is a multicenter, phase I, dose-escalation study of azacitidine followed by an open-label, phase II study.
Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
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California
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Los Angeles, California, Stati Uniti, 90033
- USC Norris Comprehensive Cancer Center
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San Diego, California, Stati Uniti, 92121
- Sidney Kimmel Cancer Center
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Maryland
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Baltimore, Maryland, Stati Uniti, 21224
- Johns Hopkins Bayview Medical Center
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Baltimore, Maryland, Stati Uniti, 21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Baltimore, Maryland, Stati Uniti, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed metastatic or unresectable NSCLC
- Patient must have failed at least one previous chemotherapy regimen
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
- Life expectancy of greater than 12 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 (Karnofsky >= 60%)
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelet count >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT] and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients who have a major objective response to treatment on this protocol, and who experience progression of disease at least 1 year after completion of protocol consent and therapy, may be re-treated at the previously effective dose and schedule
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with uncontrolled brain metastases; patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with liver metastases that replace greater than 30% of the liver parenchyma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-AZA, mannitol or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Phase I - 30mg/m2 Azacitidine
Patients receive Azacitidine 30mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.
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Azacitidine 30mg/m2 subcutaneously (SQ)
Altri nomi:
7mg by mouth (PO) on days 3 and 10 of each cycle
Altri nomi:
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Sperimentale: Phase I - 40mg/m2 Azacitidine
Patients receive azacitidine 40mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.
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7mg by mouth (PO) on days 3 and 10 of each cycle
Altri nomi:
Azacitidine 40mg/m2 SQ
Altri nomi:
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Sperimentale: Phase II Arm
Patients receive azacitidine 40mg/m2 subcutaneously (SQ) on days 1-6 and 8-10 and entinostat 7mg PO on days 3 and 10.
Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
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7mg by mouth (PO) on days 3 and 10 of each cycle
Altri nomi:
Azacitidine 40mg/m2 SQ
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
(Phase I) Maximum Tolerated Dose (MTD) of Azacitidine When Given Together With Entinostat as Determined by Number of Participants Experiencing Dose-limiting Toxicity (DLT)
Lasso di tempo: Up to 28 days
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DLT is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
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Up to 28 days
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(Phase II) Objective Response Rate After Treatment With Azacitidine and Entinostat as Assessed by Number of Participants With Response After at Least One Cycle of Therapy
Lasso di tempo: Up to 8 years
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Number of participants with progressive disease (PD), stable disease (SD), complete response (CR), or partial response (PR), as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0), after completing at least one cycle of therapy.
Per RECIST 1.0, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR is defined as >=30% decrease in the sum of the longest diameter of target lesions, CR is defined as the disappearance of all target lesions.
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Up to 8 years
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Effect of Entinostat and Azacitidine on DNA Methylation and Response
Lasso di tempo: Baseline and days 10 and 29
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Number of participants with decrease in DNA methylation ("methylation-signature positive") on Day 10 or Day 29, and either stable disease or objective response (OR) as defined by RECIST 1.0.
Per RECIST 1.0, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR is defined as >=30% decrease in the sum of the longest diameter of target lesions, complete response is defined as disappearance of all target lesions; OR=CR+PR.
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Baseline and days 10 and 29
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Major Objective Response After Immediate Subsequent Therapy as Measured by Number of Participants With PR, SD, PD After at Least 1 Cycle of Subsequent Chemotherapy
Lasso di tempo: Up to 8 years
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Number of participants with progressive disease (PD), stable disease (SD), or partial response (PR), as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) after at least 1 cycle of subsequent chemotherapy.
Per RECIST 1.0, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR is defined as >=30% decrease in the sum of the longest diameter of target lesions.
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Up to 8 years
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Overall Survival
Lasso di tempo: Up to 1 year
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Determined by the method determined by Kaplan and Meier.
95% confidence intervals will be estimated.
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Up to 1 year
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Pharmacokinetic Profile of Azacytidine as Measured by Tmax
Lasso di tempo: Day 1
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Time to maximal concentration of azacitidine in the blood.
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Day 1
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Progression-free Survival
Lasso di tempo: Up to 1 year
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Determined by the method determined by Kaplan and Meier.
95% confidence intervals will be estimated.
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Up to 1 year
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Pharmacokinetic Profile of Azacitidine as Measured by Cmax
Lasso di tempo: Day 1
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Maximal concentration (ng/mL) of azacitidine
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Day 1
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Pharmacokinetic Profile of Azacitidine as Measured by AUC (ng*hr/mL)
Lasso di tempo: Day 1
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Day 1
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Average Steady State Trough Concentration (ng/mL) of Entinostat
Lasso di tempo: Day 10 and 17
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Day 10 and 17
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Pharmacokinetic Profile of Azacitidine as Measured by Half-life
Lasso di tempo: Day 1
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Day 1
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: John Wrangle, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Processi patologici
- Malattie delle vie respiratorie
- Neoplasie
- Malattie polmonari
- Neoplasie per sede
- Attributi della malattia
- Neoplasie delle vie respiratorie
- Neoplasie toraciche
- Carcinoma, broncogeno
- Neoplasie bronchiali
- Neoplasie polmonari
- Carcinoma, polmone non a piccole cellule
- Ricorrenza
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Azacitidina
- Inibitori dell'istone deacetilasi
- Entinostat
Altri numeri di identificazione dello studio
- NCI-2009-00220 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))
- P30CA006973 (Sovvenzione/contratto NIH degli Stati Uniti)
- U01CA070095 (Sovvenzione/contratto NIH degli Stati Uniti)
- 7759 (Altro identificatore: CTEP)
- CDR0000504083 (Altro identificatore: Clinical Data Repository)
- NA_00003114 (Altro identificatore: Johns Hopkins IRB)
- J0658 (Altro identificatore: SKCCC)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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