- ICH GCP
- US-Register für klinische Studien
- Klinische Studie 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
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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California
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Los Angeles, California, Vereinigte Staaten, 90033
- USC Norris Comprehensive Cancer Center
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San Diego, California, Vereinigte Staaten, 92121
- Sidney Kimmel Cancer Center
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Maryland
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Baltimore, Maryland, Vereinigte Staaten, 21224
- Johns Hopkins Bayview Medical Center
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Baltimore, Maryland, Vereinigte Staaten, 21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Baltimore, Maryland, Vereinigte Staaten, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
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-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: 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)
Andere Namen:
7mg by mouth (PO) on days 3 and 10 of each cycle
Andere Namen:
|
Experimental: 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
Andere Namen:
Azacitidine 40mg/m2 SQ
Andere Namen:
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Experimental: 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
Andere Namen:
Azacitidine 40mg/m2 SQ
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
(Phase I) Maximum Tolerated Dose (MTD) of Azacitidine When Given Together With Entinostat as Determined by Number of Participants Experiencing Dose-limiting Toxicity (DLT)
Zeitfenster: 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
Zeitfenster: Up to 8 years
|
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.
|
Up to 8 years
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Effect of Entinostat and Azacitidine on DNA Methylation and Response
Zeitfenster: 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
Zeitfenster: 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
|
Overall Survival
Zeitfenster: 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
Zeitfenster: Day 1
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Time to maximal concentration of azacitidine in the blood.
|
Day 1
|
Progression-free Survival
Zeitfenster: Up to 1 year
|
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
Zeitfenster: 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)
Zeitfenster: Day 1
|
Day 1
|
|
Average Steady State Trough Concentration (ng/mL) of Entinostat
Zeitfenster: 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
Zeitfenster: Day 1
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Day 1
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: John Wrangle, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Pathologische Prozesse
- Erkrankungen der Atemwege
- Neubildungen
- Lungenkrankheit
- Neubildungen nach Standort
- Krankheitsattribute
- Neubildungen der Atemwege
- Thoraxneoplasmen
- Karzinom, bronchogen
- Bronchiale Neubildungen
- Lungentumoren
- Karzinom, nicht-kleinzellige Lunge
- Wiederauftreten
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Azacitidin
- Histon-Deacetylase-Inhibitoren
- Entinostat
Andere Studien-ID-Nummern
- NCI-2009-00220 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- P30CA006973 (US NIH Stipendium/Vertrag)
- U01CA070095 (US NIH Stipendium/Vertrag)
- 7759 (Andere Kennung: CTEP)
- CDR0000504083 (Andere Kennung: Clinical Data Repository)
- NA_00003114 (Andere Kennung: Johns Hopkins IRB)
- J0658 (Andere Kennung: SKCCC)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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