Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery

14 gennaio 2019 aggiornato da: National Cancer Institute (NCI)

Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care

This study combines the deoxyribonucleic acid (DNA) methyltransferase inhibitor, 5-azacitidine (5-AZA), with an orally bioavailable histone deacetylase inhibitor, entinostat (SNDX-275), for the adjuvant treatment of patients with resected stage I non-small cell lung cancer (NCSLC).

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

PRIMARY OBJECTIVES:

I. To assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage I non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage I non-small cell lung cancer.

II. To explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage I non-small cell lung cancer.

III. To assess the pharmacodynamic effects of 5-azacitidine and entinostat on DNA methylation and gene re-expression in patients with resected stage I NSCLC through analysis of sputum.

IV. To estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with N2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated.

V. To establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor DNA.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10 and entinostat orally (PO) once daily (QD) on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive standard of care.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

13

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • California
      • Los Angeles, California, Stati Uniti, 90033
        • USC / Norris Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, Stati Uniti, 33612
        • Moffitt Cancer Center
    • Maryland
      • Annapolis, Maryland, Stati Uniti, 21401
        • Anne Arundel Medical Center
      • Baltimore, Maryland, Stati Uniti, 21204
        • Greater Baltimore Medical Center
      • Baltimore, Maryland, Stati Uniti, 21224
        • Johns Hopkins Bayview Medical Center
      • Baltimore, Maryland, Stati Uniti, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Stati Uniti, 15232
        • University of Pittsburgh Cancer Institute
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, Stati Uniti, 75390
        • University of Texas Southwestern Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)
  • Patients must be at least 4 weeks out from completion of surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine =< 1.5 X institutional upper limit of normal
  • The effects of entinostat and 5-azacitidine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, 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

Exclusion Criteria:

  • Patients must be within 8 weeks of completing surgery
  • Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer
  • Patients with sub-lobar resections (ie: wedge resection or segmentectomy)
  • Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-azacitidine 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 because entinostat and 5-azacitidine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or 5-azacitidine, breastfeeding should be discontinued if the mother is treated on this protocol; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat or 5-azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Arm I (azacitidine, entinostat)
Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Altro: Analisi dei biomarcatori di laboratorio
Studi correlati
Droga: Entinostat
Dato PO
Altri nomi:
  • Inibitore HDAC SNDX-275
  • SM 27-275
  • MS-275
  • SNDX-275
Droga: Azacitidina
Dato SC
Altri nomi:
  • 5AZC
  • 5-AC
  • 5-azacitidina
  • 5-AZC
  • Azacitidina
  • Azacitidina, 5-
  • Ladakamicina
  • Milosar
  • U-18496
  • Vidazza
Nessun intervento: Arm II (standard of care)
Patients receive standard of care.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Disease-free Survival (DFS)
Lasso di tempo: 3 years
The DFS hazard rate and 95% confidence interval will be reported. At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%.
3 years

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform
Lasso di tempo: Up to 2 years
The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. For this reason, 13 pts were enrolled and data was not analyzed, for which we are unable to make any conclusions or report results.
Up to 2 years
Median Disease-free Survival
Lasso di tempo: Up to 5 years
Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
Up to 5 years
Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated
Lasso di tempo: Up to 5 years
Kaplan Meier curves will be used.
Up to 5 years
Overall Survival
Lasso di tempo: Up to 5 years
Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
Up to 5 years
Presence of Methylation Patterns
Lasso di tempo: Up to 2 years
McNemar's test will be used to compare the change in methylation after treatment in sputum.
Up to 2 years
Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Lasso di tempo: Up to 5 years
Simple descriptive statistics will be utilized to display the data.
Up to 5 years

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

National Cancer Institute (NCI)

Investigatori

  • Investigatore principale: Charles Rudin, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2010

Completamento primario (Effettivo)

1 maggio 2013

Completamento dello studio (Effettivo)

1 maggio 2013

Date di iscrizione allo studio

Primo inviato

10 settembre 2010

Primo inviato che soddisfa i criteri di controllo qualità

21 settembre 2010

Primo Inserito (Stima)

23 settembre 2010

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

5 febbraio 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

14 gennaio 2019

Ultimo verificato

1 gennaio 2019

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • NCI-2012-02901 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))
  • P30CA006973 (Sovvenzione/contratto NIH degli Stati Uniti)
  • NA_00038631
  • J1037 (Altro identificatore: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
  • 8311 (Altro identificatore: CTEP)

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 .

Prove cliniche su Analisi dei biomarcatori di laboratorio

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Kuwait

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

3
Sottoscrivi