- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne 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
Przegląd badań
Status
Warunki
Interwencja / Leczenie
Szczegółowy opis
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.
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 2
- Faza 1
Kontakty i lokalizacje
Lokalizacje studiów
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California
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Los Angeles, California, Stany Zjednoczone, 90033
- USC Norris Comprehensive Cancer Center
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San Diego, California, Stany Zjednoczone, 92121
- Sidney Kimmel Cancer Center
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Maryland
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Baltimore, Maryland, Stany Zjednoczone, 21224
- Johns Hopkins Bayview Medical Center
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Baltimore, Maryland, Stany Zjednoczone, 21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Baltimore, Maryland, Stany Zjednoczone, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: 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)
Inne nazwy:
7mg by mouth (PO) on days 3 and 10 of each cycle
Inne nazwy:
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Eksperymentalny: 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
Inne nazwy:
Azacitidine 40mg/m2 SQ
Inne nazwy:
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Eksperymentalny: 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
Inne nazwy:
Azacitidine 40mg/m2 SQ
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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(Phase I) Maximum Tolerated Dose (MTD) of Azacitidine When Given Together With Entinostat as Determined by Number of Participants Experiencing Dose-limiting Toxicity (DLT)
Ramy czasowe: 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
Ramy czasowe: 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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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
---|---|---|
Effect of Entinostat and Azacitidine on DNA Methylation and Response
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: Day 1
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Day 1
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Average Steady State Trough Concentration (ng/mL) of Entinostat
Ramy czasowe: 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
Ramy czasowe: Day 1
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Day 1
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Współpracownicy i badacze
Sponsor
Śledczy
- Główny śledczy: John Wrangle, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Publikacje i pomocne linki
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Procesy patologiczne
- Choroby Układu Oddechowego
- Nowotwory
- Choroby płuc
- Nowotwory według lokalizacji
- Atrybuty choroby
- Nowotwory Układu Oddechowego
- Nowotwory klatki piersiowej
- Rak, Bronchogenny
- Nowotwory oskrzeli
- Nowotwory płuc
- Rak, płuco niedrobnokomórkowe
- Nawrót
- Molekularne mechanizmy działania farmakologicznego
- Inhibitory enzymów
- Antymetabolity, przeciwnowotworowe
- Antymetabolity
- Środki przeciwnowotworowe
- Azacytydyna
- Inhibitory deacetylazy histonowej
- Entinostat
Inne numery identyfikacyjne badania
- NCI-2009-00220 (Identyfikator rejestru: CTRP (Clinical Trial Reporting Program))
- P30CA006973 (Grant/umowa NIH USA)
- U01CA070095 (Grant/umowa NIH USA)
- 7759 (Inny identyfikator: CTEP)
- CDR0000504083 (Inny identyfikator: Clinical Data Repository)
- NA_00003114 (Inny identyfikator: Johns Hopkins IRB)
- J0658 (Inny identyfikator: SKCCC)
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .
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